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Chlamydia trachomatis exploits sphingolipid metabolic pathways during infection of phagocytes
No full textChlamydiae are obligate intracellular pathogens that utilize host cell metabolites for catabolic and anabolic processes. The bacteria replicate in epithelial cells from which they take up sphingolipids (SL) and incorporate them into the chlamydial membrane and the vacuole (termed inclusion). SL uptake is essential for Chlamydia trachomatis (Ctr) in epithelial cells; however, they can also infect phagocytes, but the consequences for the SL metabolism have not yet been investigated in these cells. We performed a quantitative sphingolipidome analysis of infected primary neutrophils, macrophages, and immortalized fallopian tube epithelial cells. Sphingosine (Sph) levels are elevated in primary M2-like macrophages and human neutrophils infected with C. trachomatis. Human neutrophils respond to the pathogen by markedly upregulating sphingosine kinase 1 (SPHK1). We show in M2-like macrophages, by RNAseq, that two counteracting pathways involving upregulation of SPHK1, but also sphingosine-1-phosphate phosphatases 1 and 2 (SGPP1 and SGPP2) and sphingosine-1-phosphate lyase (SGPL1), maintain a steady pool of S1P. Using click chemistry, we show that exogenously added sphingomyelin (SM) and ceramide (Cer) are efficiently taken up into the chlamydial inclusion and are integrated into bacterial membranes in infected M2-like macrophages. Exogenous Sph reduces chlamydial infectivity, is transported into the inclusion lumen, and integrates into chlamydial membranes, suggesting that this particular SL species could represent a host defense mechanism. Taken together, our data indicate an important role for Sph/Sph kinase vs S1P/S1P phosphatase balance in infected phagocytes and a previously unrecognized role for sphingosine in the immune defense against chlamydial infection
Transcriptomics insights into the functional role of tick Ixodes ricinus proteins metalloprotease and antigen p23
No full textIxodes ricinus ticks (Acari: Ixodidae) are hematophagous ectoparasites and a major European vector of zoonotic diseases affecting global health. Tick salivary and midgut proteins antigen p23 (A0A0K8RKR7) and metalloprotease (A0A0K8RCY8) were previously implicated in the pathophysiology of the tick-borne allergy alpha-Gal syndrome (AGS). This study aimed to functionally characterize these two biomolecules, focusing on their role in I. ricinus tick feeding and reproduction through gene knockdown by RNA interference and midgut transcriptomic analysis. Validation of RNA-seq data was conducted using RT-qPCR analysis on tick midgut and salivary gland tissues. Silencing the expression of p23 and metalloprotease did not result in any significant differences in tick engorgement and egg batch weights compared to the control group. Gene set enrichment analysis following antigen p23 gene knockdown identified significantly upregulated pathways associated with protein production and suppressed routes mostly correlated with ion transport, lipid metabolism, catalytic activity, protein modification, and G-protein activity. Partial knockdown of the metalloprotease led to the upregulation of several biological and functional pathways associated with RNA splicing and significantly suppressed routes connected with detoxification, protein modification, catalytic activity and molecule binding. Antigen p23 appears to play a functional role in tick midgut cell homeostasis, primarily by participating in regulatory and signaling processes essential for cell viability. Metalloprotease is potentially involved in regulating midgut response to oxidative stress, thereby reducing tissue damage and promoting regular cell proliferation, growth and behavior. These results provide insights into tick physiology and bases for further research on tick-host interactions and AGS pathogenesis
The use of organic binders in monumental terracruda sculpture: Integrating Sanskrit texts with spectroscopic and spectrometric data in the study of Tepe Narenj and Qol-e-tut examples (Kabul, Afghanistan, 5th to 11th centuries CE)
No full textThis work is part of a broader research project aimed at understanding the technology of making Buddhist monumental terracruda (air-dried clay) sculptures and contributing to the design of specific recovery protocols and conservation treatments for archaeological examples. Previous studies have been mainly based on information obtained through the comparative study of traditional knowledge preserved in India and petrographic, mineralogical, chemical and botanical characterization performed on Afghan examples from Buddhist sites of Tepe Narenj and Qol-e-tut (5th to 11th centuries). Here the focus is to verify the hypothesis of the addition of possible organic binding substances to elaborate the modelling pastes on the examples of Tepe Narenj and Qol-e-tut, with particular interest in the search for gums, as these compounds had been identified by analyses of other Afghan examples and their use is documented in India today for the finishing layers of the type of sculptures under study. So far, the studies that have looked for organic binders have done so with the aim of analysing painting techniques. However, ancient sacred texts (8th - 17th centuries CE) mention a wide use of organic substances also in the preparation of clays. In a pioneering approach aimed at elucidating their presence in the modelling pastes, we used a staggered analytical approach as part of a European IPERION-HS project with first, FTIR analyses to verify their inclusion and if possible, their specific groups and secondly, GC- MS analyses to characterize them. Finally, we used a structural analytical approach based on MALDI-TOF mass spectrometry to study the polysaccharides and access their taxonomic information. The results suggest that multiple organic binders were added, and the use of gums has been confirmed. Although this represents only a first step in the study of the use of organic binders in the modelling pastes and plasters of monumental terracruda sculpture, the results appear to be consistent with the complex processes described in ancient sacred literature related to their preparation
Institutions, Labor Market Inequalities, and Welfare
No full textThis dissertation consists of four independent chapters that contribute to the literature of labor and public economics. Institutions influence the labor market outcomes and redistribution of incomes, ultimately shaping the income distributions we observe today. The first chapter focuses on the legal framework for migrants on the German labor market and highlights the differences between two groups of foreign workers: citizens of EU member states and citizens of third countries. Germany’s institutions favor EU citizens in terms of mobility, leading to higher wages and higher unemployment. The second and third chapter take a broader perspective on the entire German population and how the earnings dynamics and income inequalities differ between birth cohorts – including welfare implications. The final chapter examines the German tax and transfer system and its implicit welfare weights along the income distribution.
Chapter 1 examines the difference in mobility on the German labor market for citizens of EU member states and third countries and its consequences. Immigrants from non-EU countries face considerably higher barriers. I develop a wage posting model to illustrate the underlying mechanisms and provide reduced-form evidence of the causal effects of EU citizenship on labor market outcomes. I exploit the 2004 enlargement of the European Union, which granted EU status to immigrants from ten Eastern European countries residing in Germany. Using a difference-in-differences framework as well as an event-study and rich administrative data from the Sample of Integrated Labour Market Biographies (SIAB), I compare the labor market trajectories of this group before and after enlargement with those of non-EU immigrants who did not benefit from such a change in legal status. The results show that EU citizenship increases wages while unemployment rates increase. These effects are persistent over time.
Chapter 2 puts a spotlight on the earnings dynamics of different birth cohorts in Germany. Women born later experience greater earnings growth volatility at given ages than older cohorts. This implies a welfare loss due to increased earnings risk. However, German registry data for the years 2001-2016 reveal a moderation in higher-order earnings risk: Men and women born later face higher skewness in earnings changes, indicating fewer large decreases than increases, and lower kurtosis at younger ages, implying fewer large earnings changes. These trends point at a welfare increase and remain true for 5-year earnings changes, which are more reflective of persistent changes. During the Great Recession, males' skewness dropped sharply; younger women were unaffected.
Chapter 3 examines the welfare effects of changes in real income distributions between German birth cohorts. We calculate the relative income increase at every income level of the cohort born earlier necessary to make a person behind the veil of ignorance indifferent between being born into either cohort. With relatively low risk aversion, individuals born in the 1970s are on average better off with respect to labor earnings than those born in the 1960s and individuals born in the 1980s enjoy higher welfare than those born in the 1970s. At higher levels of risk aversion, the welfare gain diminishes, implying that increased earnings inequality offset much of the gain of increased average earnings. However, redistribution through households and the welfare state cushioned much of the increase in inequality. Focusing on post-government household income instead of individual labor earnings, for both women and men, the proportional income increase for the earlier cohort for someone to be indifferent between being born in the earlier or the later cohort is substantially larger, especially at higher degrees of relative risk aversion.
Chapter 4 investigates the question: How much does society value redistribution? The common method to derive inverse-optimum welfare weights is by inverting an optimal-tax model. Our alternative imposes fewer restrictions on labor supply and enables comparisons across household types. We use a structural labor supply model to calculate the marginal value of public funds for various small tax reductions, directly linked to welfare weights. An application to Germany finds: i) The tax-transfer system is optimal if society values one additional Euro for the bottom decile three times as much as for the median. ii) At low-medium incomes, weights for couples exceed those for singles substantially.Diese Dissertation besteht aus vier unabhängigen Kapiteln, die einen Beitrag zur Literatur der Arbeitsmarktökonomie und der öffentlichen Finanzen leisten. Institutionen beeinflussen die Arbeitsmarktergebnisse und die Umverteilung von Einkommen und prägen letztlich die Einkommensverteilungen, die wir heute beobachten. Das erste Kapitel befasst sich mit dem rechtlichen Rahmen für Migranten auf dem deutschen Arbeitsmarkt und hebt die Unterschiede zwischen zwei Gruppen von ausländischen Arbeitskräften hervor: Bürger von EU-Mitgliedstaaten und Bürger von Drittstaaten. Die deutschen Institutionen begünstigen EU-Bürger in Bezug auf Mobilität, was zu höheren Löhnen, aber auch höherer Arbeitslosigkeit führt. Das zweite und dritte Kapitel nehmen eine breitere Perspektive auf die gesamte deutsche Bevölkerung ein und untersuchen, wie sich Verdienstentwicklungen und Einkommensungleichheiten zwischen Geburtskohorten unterscheiden – einschließlich ihrer Wohlfahrtsimplikationen. Das letzte Kapitel analysiert das deutsche Steuer- und Transfersystem und seine impliziten Wohlfahrtsgewichte entlang der Einkommensverteilung.
Kapitel 1 untersucht die Unterschiede in der Arbeitsmarktmobilität zwischen Bürgern von EU-Mitgliedstaaten und Drittstaaten sowie deren Konsequenzen. Einwanderer aus Nicht-EU-Ländern stehen vor deutlich höheren Hürden. Ich entwickle ein Lohnangebotsmodell, um die zugrunde liegenden Mechanismen zu veranschaulichen, und präsentiere Schätzungen in reduzierter Form von kausalen Effekten der EU-Staatsbürgerschaft auf Arbeitsmarktergebnisse. Dabei nutze ich die EU-Erweiterung des Jahres 2004, die Einwanderern aus zehn osteuropäischen Ländern, die in Deutschland lebten, den EU-Status verlieh. Mit einem Differenz-von-Differenzen-Ansatz sowie einer Ereignisstudie und unter Verwendung von administrativen Daten aus der Stichprobe der Integrierten Arbeitsmarktbiografien (SIAB) vergleiche ich die Arbeitsmarktverläufe dieser Gruppe vor und nach der Erweiterung mit denen von Nicht-EU-Einwanderern, die nicht von einer solchen Statusänderung profitierten. Die Ergebnisse zeigen, dass die EU-Staatsbürgerschaft die Löhne erhöht, jedoch auch die Arbeitslosigkeit steigen lässt. Diese Effekte bleiben langfristig bestehen.
Kapitel 2 richtet den Fokus auf die Einkommensdynamik unterschiedlicher Geburtskohorten in Deutschland. Frauen späterer Jahrgänge erfahren im gleichen Alter eine größere Schwankungsbreite im Einkommenswachstum als ältere Kohorten. Dies impliziert einen Wohlfahrtsverlust aufgrund eines höheren Einkommensrisikos. Allerdings zeigen deutsche Registerdaten für die Jahre 2001 bis 2016 eine Abschwächung von Einkommensrisiken höherer Ordnung: Männer und Frauen späterer Jahrgänge haben bei Einkommensänderungen eine höhere Schiefe, die weniger große Einkommensgefälle als -anstiege anzeigt, und in jüngeren Jahren eine geringere Wölbung, die weniger extreme Einkommensänderungen impliziert. Diese Trends deuten auf einen Wohlfahrtsgewinn hin und gelten auch für Einkommensänderungen über fünf Jahre, die eher persistente Veränderungen widerspiegeln. Während der Finanzkrise sank die Schiefe für Männer stark; junge Frauen blieben weitgehend unbeeinflusst.
Kapitel 3 analysiert die Wohlfahrtseffekte von Veränderungen in den realen Einkommensverteilungen zwischen deutschen Geburtskohorten. Wir berechnen den relativen Einkommensanstieg auf jedem Einkommensniveau der älteren Kohorte, der erforderlich wäre, um eine Person hinter einem Schleier des Nichtwissens indifferent zwischen einer Geburt in der früheren oder in der späteren Kohorte zu machen. Bei relativ geringer Risikoaversion sind Personen, die in den 1970er-Jahren geboren wurden, im Durchschnitt besser gestellt als jene, die in den 1960er-Jahren geboren wurden, und Personen der 1980er-Jahrgänge weisen eine höhere Wohlfahrt auf als die der 1970er-Jahrgänge. Bei höherer Risikoaversion verringert sich der Wohlfahrtsgewinn jedoch, da zunehmende Einkommensungleichheit einen Großteil des Zuwachses aus höheren Durchschnittseinkommen neutralisiert. Umverteilung durch Haushalte und den Wohlfahrtsstaat hat jedoch einen großen Teil der Ungleichheit abgefedert. Betrachtet man statt individueller Arbeitseinkommen die verfügbaren Haushaltseinkommen nach Steuern und Transfers, ergibt sich sowohl für Frauen als auch für Männer, dass der erforderliche Einkommensanstieg der früheren Kohorte deutlich höher ausfällt, insbesondere bei stärkerer Risikoaversion.
Kapitel 4 widmet sich der Frage: Wie stark bewertet die Gesellschaft Umverteilung? Das gängige Verfahren, inverse optimale Wohlfahrtsgewichte herzuleiten, besteht darin, ein Optimalsteuermodell umzukehren. Unser alternativer Ansatz unterliegt weniger Restriktionen in Bezug auf das Arbeitsangebot und ermöglicht Vergleiche zwischen Haushaltstypen. Wir nutzen ein strukturelles Arbeitsangebotsmodell, um den marginalen Wert öffentlicher Mittel für verschiedene kleine Steuersenkungen zu berechnen, die direkt mit Wohlfahrtsgewichten verknüpft sind. Eine Anwendung auf Deutschland zeigt: i) Das Steuer- und Transfersystem ist dann optimal, wenn die Gesellschaft einen zusätzlichen Euro für das unterste Dezil dreimal so hoch bewertet wie für den Median. ii) Bei niedrigen bis mittleren Einkommen liegen die Gewichte für Paare deutlich über denen für Alleinstehende
Framing geplünderter Kulturgüter
No full textLooting and trafficking of archaeological objects is a worldwide problem, which often becomes more severe during armed conflicts – two examples being the looting of Iraqi museums and archaeological sites after 2003, and the plunder of Syrian heritage during the civil war. Shocking images of archaeological destruction have attracted significant media attention in so-called ‘Western’ countries. In some situations, the reporting of European news media on the obliteration of what is perceived as ‘world heritage’ can even inspire public outrage. Between 2014 and 2015, the shock value of cultural destruction wrought by the terror group IS was used to draw attention to conflict-related antiquities trafficking, portraying the illicit antiquities market as a main income source for the terrorists. This sensationalist reporting has roused public concern and arguably even led to a moral panic. The antiquities market has reacted defensively to this portrayal, and used the overblown figures and tenuous allegations of terror financing seen in the media to discredit research into and regulation of the antiquities trade. In this paper, I discuss the consequences of this discourse and the continuing lack of voices from Western Asia therein.Raubgrabungen und der illegale Handel mit archäologischen Funden ist ein andauerndes weltweites Problem, das sich in bewaffneten Konflikten verstärkt – zwei Beispiele dafür sind die Plünderung irakischer Museen und Aus-grabungsstätten nach 2003 und der Raubbau an syrischen Kulturgütern im Bürgerkrieg. Schockierende Bilder von der Zerstörung archäologischen Kulturerbes erregen mitunter große Medienaufmerksamkeit in sogenannten ‚west-lichen‘ Ländern. Bisweilen können Berichte europäischer Medien über die Vernichtung von als ‚Weltkulturerbe‘ verstandenen Altertümern sogar öffentliche Empörung auslösen. Zwischen 2014 und 2015 wurde der Schockwert der Kulturzerstörung durch die Terrorgruppe IS genutzt, um Aufmerksamkeit für das Problem von Raubgrabun-gen im Rahmen bewaffneter Konflikte zu erregen, indem der Antikenhandel als eine der Haupteinnahmequellen der Terrorgruppe dargestellt wurde. Dieser reißerische Journalismus hat öffentliche Besorgnis erregt und mag sogar eine moral panic verursacht haben. Der Antikenhandel selbst hat defensiv auf diese Darstellung reagiert und die übertriebenen Zahlen und schwer zu beweisenden Anschuldigungen der Terrorfinanzierung genutzt, um Erforschung und Regulierung des Marktes zu diskreditieren. In diesem Artikel beschreibe ich die Konsequenzen dieses Diskurses, und das Fehlen von Stimmen aus den betroffenen Ländern darin
Evidence for a Unifying NiI/NiIII Mechanism in Light-Mediated Cross-Coupling Catalysis
No full textAdvances in nickel catalysis have significantly broadened the synthetic chemists’ toolbox, particularly through methodologies leveraging paramagnetic nickel species via photoredox catalysis or electrochemistry. Key to these reactions is the oxidation state modulation of nickel via single-electron transfer events. Recent mechanistic studies indicate that C(sp2)–heteroatom bond formations proceed through NiI/NiIII cycles. Related C(sp2)–C(sp3) cross-couplings operate via the photocatalytic generation of C-centered radicals and a catalytic cycle that involves Ni0, NiI, and NiIII species. Here, we show that light-mediated nickel-catalyzed C(sp2)–C(sp3) bond formations can be carried out without using exogenous photoredox catalysts but with a photoactive ligand. In a pursuit of expanding the scope of C(sp2)–heteroatom couplings using donor–acceptor ligands, we identified a photoactive nickel complex capable of catalyzing cross-couplings between aryl halides and benzyltrifluoroborate salts. Mechanistic investigations provide evidence that transmetalation between a photochemically generated NiI species and the organoboron compound is the key catalytic step in a NiI/NiIII catalytic cycle under these conditions
Recurrence affects the geometry of visual representations across the ventral visual stream in the human brain
No full textThe human brain orchestrates object vision through an interplay of feedforward processing in concert with recurrent processing. However, where, when, and how recurrent processing contributes to visual processing is incompletely understood due to the difficulties in teasing apart feedforward and recurrent processing. We combined a backward masking paradigm with multivariate analysis on EEG and fMRI data to isolate and characterize the nature of recurrent processing. We find that recurrent processing substantially shapes visual representations across the ventral visual stream, starting early on at around 100 ms in early visual cortex (EVC) and two later phases of around 175 and 300 ms in lateral occipital cortex (LOC), adding persistent rather than transient neural dynamics to visual processing. Using convolutional neural network models for comparison with the brain, we show that recurrence changes the feature format in LOC from predominantly mid-level to more high-level features. Finally, we show that recurrence is mediated by four distinct spectro-temporal neural components, which span the theta to beta frequency range. Together, our results reveal the nature and mechanisms of the effects of recurrent processing on the visual representations in the human brain
Über die Geschichte der Bärentraube, der arzneilichen Anwendung ihrer Blätter, (Fol. uvae ursi) und ihre neueren Präparate
No full textDigitalisat der Ausgabe von 1929, erschienen 202
Dye-sensitized upconversion nanoparticles with enhanced aqueous luminescence for neuronal imaging
No full textThe combination of organic dyes as photosensitizers with inorganic upconversion nanoparticles (UCNPs) has significantly enhanced upconversion luminescence when excited with near-infrared (NIR) light. Additionally, by employing surface functionalization techniques, a high signal-to-noise ratio can be achieved, resulting in exceptional resolution for bioimaging. The objective of our study was to develop a heptamethylcyanine derivative (IR61-BF) for dye-sensitized UCNPs, enhancing their luminescence efficiency in aqueous solutions. This was done by introducing a difluorobenzene group into the cyanine structure. Rare earth-doped UCNPs with a core–shell structure, NaYF4:YbTm@NaYF4:YbNd, were synthesized using a high-temperature decomposition method. In this structure, the Nd3+ ions function as efficient sensitizers by absorbing 808 nm NIR light. To further enhance the upconversion efficiency, the molecular structure of the NIR dye IR61 was optimized. By integrating a difluorinated phenyl group into the cyanine backbone, we significantly increased the fluorescence quantum yield of the dye and enhanced the dye sensitization effect of the UCNPs. Subsequently, the UCNPs were coated with an amphiphilic ligand, DSPE-PEG, and IR61-BF was incorporated into the hydrophobic region between the UCNPs, and a remarkable 167.1-fold enhancement in upconversion luminescence in the aqueous phase was achieved. Their biocompatibility for neuronal imaging was evaluated using NSC34, Neuro2a, and C6 glioma cells, while their potential for retrograde intra-neuronal delivery was confirmed by using a microfluidic model of cortical neurons. We demonstrated that the newly synthesized heptamethine cyanine derivative IR61-BF shows exceptional sensitization of UCNPs due to the incorporation of a difluorobenzene group, particularly in aqueous solutions