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Of the hepatic cell lines developed for in vitro studies of hepatic functions as alternatives to primary human hepatocytes, many have lost major liver-like functions, but not HepaRG cells. The increasing use of the latter worldwide raises the need for establishing the reference functional status of early biobanked HepaRG cells. Using deep proteome and secretome analyses, the levels of master regulators of the hepatic phenotype and of the structural elements ensuring biliary polarity were found to be close to those in primary hepatocytes. HepaRG cells proved to be highly differentiated, with functional mitochondria, hepatokine secretion abilities, and an adequate response to insulin. Among differences between primary human hepatocytes and HepaRG cells, the factors that possibly support HepaRG transdifferentiation properties are discussed. The HepaRG cell system thus appears as a robust surrogate for primary hepatocytes, which is versatile enough to study not only xenobiotic detoxification, but also the control of hepatic energy metabolism, secretory function and disease-related mechanisms.
We analyze debt and debt management of Americans nearing retirement age. We show that older people have numerous financial obligations that can lead to financial distress. Using data from the 2015 National Financial Capability Study and an extensive literature review, we show that lack of financial literacy, lack of information, and behavioral biases help explain the prevalence of debt later in life. Our evidence indicates that debt at older ages can negatively influence retirement well-being.
Den Visitationen am Reichskammergericht (RKG) wurden in letzter Zeit zwei unterschiedliche wissenschaftliche Untersuchungen gewidmet. Während Alexander Denzler den Aussagewert medialer Schriftkultur im "Schriftalltag" am Beispiel der letzten Visitation des RKGs (1767–1776) untersucht hat,1 widmet sich Anette Baumann als quellenversierte langjährige Leiterin der "Forschungsstelle der Gesellschaft für Reichskammergerichtsforschung" in Wetzlar den Visitationen von 1529–1588.2 Sie werden von ihr als "Expertentreffen" von Juristen interpretiert, die auch für das Verfassungsverständnis im Alten Reich bedeutsam sind. Das tragende Quellenmaterial bildet – neben einschlägiger Sekundärliteratur – vor allem der reiche Korrespondenz- und Aktenbestand im Wiener Haus-, Hof- und Staatsarchiv in Gestalt von Visitationsabschieden, Protokollen, Korrespondenzen, Vollmachten, Gutachten, Voten, Ladungen, Instruktionen, Gravamina, Fragebögen, persönlichen Notizen, Schreiben, Berichten und Augenscheinkarten,3 die das analysierte Schriftgut der Visitationen repräsentieren. Mit Hilfe einer erstellten Datenbank, die übrigens verschiedenen Forschungsinstitutionen – darunter auch dem MPI für europäische Rechtsgeschichte – zur Verfügung steht, ist es Baumann möglich, in den Beständen gezielt "nach Visitationsbelangen zu suchen" (17). Ziel ihrer gründlichen Untersuchung ist es, die Arbeit der Visitationskommission (VK) in dem "komplexen Kommunikationsprozess" (5) aufzuhellen, in dessen Mittelpunkt die VK stand – eingebettet in das Beziehungsgeflecht zwischen Kaiser, Reichsständen, Reichstag und Reichskammergericht (RKG). Durch die Reichskammergerichtsordnung von 1521 war die Kommission erstmals als "Visitation" reichsgesetzlich eingesetzt worden, um als Kontrollorgan einerseits das RKG finanziell zu sichern und andererseits die Abstellung von "Gebrechen" zu garantieren, d.h. das Gericht arbeitsfähig zu machen und zu erhalten. Die VK war somit eine Institution des Alten Reiches, die ursprünglich zur jährlichen Kontrolle bestimmt war. Eingesetzt von Kaiser und Reichsständen stand sie im Spannungsverhältnis politischer und konfessioneller Konstellationen auf dem Reichstag. Folgerichtig legt Baumann ihre Untersuchung auch weniger als Institutionengeschichte an, sondern als eine Darstellung von Reichsverfassungspraxis am Beispiel der VK. Aus dem reichen Archivmaterial werden die "Kommunikationsprozesse" herausdestilliert, um auf verfassungsmäßige Regelhaftigkeiten als Ordnungskategorien der Visitationsverfahren schließen zu können. Dabei stellt sich immer die Frage, ob die beobachteten Verfahren zu rechtlicher "Verfassung" geronnen sind oder sich noch im vorrechtlichen Raum ritualisierter Verfasstheit bewegen. So gesehen bietet das geschilderte Geschehen um die und in der VK einen Blick in das Laboratorium über die Entwicklung rechtlicher und politischer Regelungs- und Verfassungsprozesse. ...
Over the life-cycle, wealth holdings tend to be highest in the early part of retirement. The quality of financial decisions among older adults is therefore an important determinant of their financial security during the asset drawdown phase. This paper assesses how financial literacy shapes financial decision-making at older ages. We devised a special module in the Singapore Life Panel survey to measure financial literacy to study its relationship with three aspects of household financial and investment behaviors: credit card debt repayment, stock market participation, and adherence to age-based investment glide paths. We found that the majority of respondents age 50+ has some grasp of concepts such as interest compounding and inflation, but fewer know about risk diversification. We provide evidence of a statistically significant positive association between financial literacy and each of the three aspects of suboptimal financial decision-making, controlling for many other factors, including education. A one-unit increase in the financial literacy score was associated with an 8.3 percentage point greater propensity to hold stocks, and a 1.7 percentage point higher likelihood of following an age-appropriate investment glide path. The financial literacy score is only weakly positively linked with timely credit card balance repayment, both in terms of statistical significance and estimate size.
This collection edited by Dave De ruysscher, Albrecht Cordes, Serge Dauchy and Heikki Pihlajamäki considers what size or varieties of business were considered to be the best. The answer to this question depends on the time period under examination, and it also differs between jurisdictions. The chapters in the collection take a broad approach as they collectively cover a long time span and have a wide geographical spread. They consider examples from the Middle Ages, the early modern period and the 19th century. The places examined here are now in the jurisdictions of Germany, Italy, Belgium, Spain and England. As a whole, the chapters address some of the tension between the perceived advantages and disadvantages of big business against the small and medium enterprises (SMEs) and also the limited liability corporation in comparison to the unlimited liability partnership form. The edited collection takes a deliberately integrative approach, as it combines concepts and ideas from legal studies with those of economic history, business studies and comparative political analysis. ...
Many Americans claim Social Security benefits early, though this leaves them with lower benefits throughout retirement. We build a lifecycle model that closely tracks claiming patterns under current rules, and we use it to predict claiming delays if, by delaying benefits, people received a lump sum instead of an annuity. We predict that current early claimers would defer claiming by a year given actuarially fair lump sums, and the predictions conform with respondents’ answers to a strategic survey about the lump sum. In other words, such a reform could provide an avenue for encouraging delayed retirement without benefit cuts or tax increases. Moreover, many people would still defer claiming even for smaller lump sums.
We show that firm liability structure and associated cash flow matter for firm behavior, and that financial market participants price stocks accordingly. Looking at firm level stock price changes around monetary policy announcements, we find that firms that have more cash flow exposure see their stock prices affected more. The stock price reaction depends on the maturity and type of debt issued by the firm, and the forward guidance provided by the Fed. This effect has remained intact during the ZLB period. Importantly, we show that the effect is not a rule of thumb behavior outcome and that the marginal stock market participant actually studies and reacts to the liability structure of firm balance sheets. The cash flow exposure at the time of monetary policy actions predicts future net worth, investment, and assets, verifying the stock pricing decision and also providing evidence of cash flow effects on firms' real behavior. The results hold for S&P500 firms that are usually thought of not being subject to tight financial constraints.
A common prediction of macroeconomic models of credit market frictions is that the tightness of financial constraints is countercyclical. As a result, theory implies a negative collateralizability premium; that is, capital that can be used as collateral to relax financial constraints provides insurance against aggregate shocks and commands a lower risk compensation compared with non-collateralizable assets. We show that a longshort portfolio constructed using a novel measure of asset collateralizability generates an average excess return of around 8% per year. We develop a general equilibrium model with heterogeneous firms and financial constraints to quantitatively account for the collateralizability premium.
Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis
(2019)
Background: Prostanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated.
Methods: Therefore, we used pro-thrombotic venous milieu generation by bare metal stent transjugular intrahepatic portosystemic shunt insertion, to study the role of prostanoids in decompensated liver cirrhosis. Here, 89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein.
Results: While the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein (all P<0.0001). Baseline concentrations of thromboxane B2 in the portal vein were independently associated with an increase of portal hepatic venous pressure gradient during short term follow-up, as an indirect sign of thrombogenic potential (multivariable P = 0.004). Moreover, severity of liver disease was inversely correlated with portal as well as hepatic vein levels of prostaglandin D2 and E2 (all P<0.0001).
Conclusions: Elevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis.
Trial registration: ClinicalTrials.gov identifier: NCT03584204.
Aims: The examination of histological sections is still the gold standard in diagnostic pathology. Important histopathological diagnostic criteria are nuclear shapes and chromatin distribution as well as nucleus-cytoplasm relation and immunohistochemical properties of surface and intracellular proteins. The aim of this investigation was to evaluate the benefits and drawbacks of three-dimensional imaging of CD30+ cells in classical Hodgkin Lymphoma (cHL) in comparison to CD30+ lymphoid cells in reactive lymphoid tissues.
Materials and results: Using immunoflourescence confocal microscopy and computer-based analysis, we compared CD30+ neoplastic cells in Nodular Sclerosis cHL (NScCHL), Mixed Cellularity cHL (MCcHL), with reactive CD30+ cells in Adenoids (AD) and Lymphadenitis (LAD). We confirmed that the percentage of CD30+ cell volume can be calculated. The amount in lymphadenitis was approx. 1.5%, in adenoids around 2%, in MCcHL up to 4,5% whereas the values for NScHL rose to more than 8% of the total cell cytoplasm. In addition, CD30+ tumour cells (HRS-cells) in cHL had larger volumes, and more protrusions compared to CD30+ reactive cells. Furthermore, the formation of large cell networks turned out to be a typical characteristic of NScHL.
Conclusion: In contrast to 2D histology, 3D laser scanning offers a visualisation of complete cells, their network interaction and spatial distribution in the tissue. The possibility to differentiate cells in regards to volume, surface, shape, and cluster formation enables a new view on further diagnostic and biological questions. 3D includes an increased amount of information as a basis of bioinformatical calculations.
Natural history collections are fundamental for biodiversity research as well as for any applied environment-related research. These collections can be seen as archives of earth´s life providing the basis to address highly relevant scientific questions such as how biodiversity changes in certain environments, either through evolutionary processes in a geological timescale, or by man-made transformation of habitats throughout the last decades and/or centuries. A prominent example is the decline of the European flat oyster Ostrea edulis Linneaus, 1758 in the North Sea and the concomitant invasion of the common limpet slipper Crepidula fornicata, which has been implicated to have negative effects on O. edulis. We used collections to analyse population changes in both species in the North Sea. In order to reconstruct the change in distribution and diversity over the past 200 years, we combined the temporal and spatial information recorded with the collected specimens contained in several European natural history collections. Our data recover the decline of O. edulis in the North Sea from the 19th century to the present and the process of invasion of C. fornicata. Importantly, the decline of O. edulis was nearly completed before C. fornicata appeared in the North Sea, suggesting that the latter had nothing to do with the local extinction of O. edulis in the North Sea.
Klar scheinen die Berge vor dem nachtblauen Himmel. Ihre sanften Wölbungen geben in ihrer Mitte den Blick frei auf einen hell leuchtenden Stern. Die Landschaft ist ausgestorben, der Boden von Schnee bedeckt, die aus ihm herausragenden Bäume karg und ausgedörrt. Der einzige Abdruck menschlicher Existenz ist kaum sichtbar. Er zeigt sich in einem kleinen Kreuz an der Spitze des höchsten Berges. Doch die Szenerie hat nichts Bedrohliches oder gar Trauriges an sich, vielmehr strahlt das Gemälde eine inhärente Ruhe aus. Die Komposition ist harmonisch, die Anwendung verschiedener Nuancen von Blau tragen zur Ausgewogenheit bei. Bei der Betrachterin hinterlässt die dargestellte Landschaft, trotz ihrer Kargheit, den Eindruck einer Vollkommenheit der Natur. ...
Visual aesthetic experiences unfold over time, yet most of our understanding of such experiences comes from experiments using static visual stimuli and measuring static responses. Here, we investigated the temporal dynamics of subjective aesthetic experience using temporally extended stimuli (movie clips) in combination with continuous behavioral ratings. Two groups of participants, a rate group (n = 25) and a view group (n = 25), watched 30-second video clips of landscapes and dance performances in test and retest blocks. The rate group reported continuous ratings while watching the videos, with an overall aesthetic judgment at the end of each video, in both test and retest blocks. The view group, however, passively watched the videos in the test block, reporting only an overall aesthetic judgment at the end of each clip. In the retest block, the view group reported both continuous and overall judgments. When comparing the two groups, we found that the task of making continuous ratings did not influence overall ratings or agreement across participants. In addition, the degree of temporal variation in continuous ratings over time differed substantially by observer (from slower "integrators" to "fast responders"), but less so by video. Reliability of continuous ratings across repeated exposures was in general high, but also showed notable variance across participants. Together, these results show that temporally extended stimuli produce aesthetic experiences that are not the same from person to person, and that continuous behavioral ratings provide a reliable window into the temporal dynamics of such aesthetic experiences while not materially altering the experiences themselves.
Cardiovascular diseases are the most prominent cause of death in Western society, especially in the elderly. With the increasing life expectancy, the number of patients with cardiovascular diseases will rise in the near future, leading to an increased healthcare burden. There is a need for new therapies to treat this growing number of patients. The discovery of long non-coding RNAs has led to a novel group of molecules that could be considered for their potential as therapeutic targets. This review presents an overview of long non-coding RNAs that are regulated in vascular disease and aging and which might therefore give insight into new pathways that could be targeted to diagnose, prevent, and/or treat vascular diseases.
Chaperone-assisted selective autophagy (CASA) initiated by the cochaperone Bcl2-associated athanogene 3 (BAG3) represents an important mechanism for the disposal of misfolded and damaged proteins in mammalian cells. Under mechanical stress, the cochaperone cooperates with the small heat shock protein HSPB8 and the cytoskeleton-associated protein SYNPO2 to degrade force-unfolded forms of the actin-crosslinking protein filamin. This is essential for muscle maintenance in flies, fish, mice and men. Here, we identify the serine/threonine protein kinase 38 (STK38), which is part of the Hippo signaling network, as a novel interactor of BAG3. STK38 was previously shown to facilitate cytoskeleton assembly and to promote mitophagy as well as starvation and detachment induced autophagy. Significantly, our study reveals that STK38 exerts an inhibitory activity on BAG3-mediated autophagy. Inhibition relies on a disruption of the functional interplay of BAG3 with HSPB8 and SYNPO2 upon binding of STK38 to the cochaperone. Of note, STK38 attenuates CASA independently of its kinase activity, whereas previously established regulatory functions of STK38 involve target phosphorylation. The ability to exert different modes of regulation on central protein homeostasis (proteostasis) machineries apparently allows STK38 to coordinate the execution of diverse macroautophagy pathways and to balance cytoskeleton assembly and degradation.
The long-awaited detection of a gravitational wave from the merger of a binary neutron star in August 2017 (GW170817) marks the beginning of the new field of multi-messenger gravitational wave astronomy. By exploiting the extracted tidal deformations of the two neutron stars from the late inspiral phase of GW170817, it is now possible to constrain several global properties of the equation of state of neutron star matter. However, the most interesting part of the high density and temperature regime of the equation of state is solely imprinted in the post-merger gravitational wave emission from the remnant hypermassive/supramassive neutron star. This regime was not observed in GW170817, but will possibly be detected in forthcoming events within the current observing run of the LIGO/VIRGO collaboration. Numerous numerical-relativity simulations of merging neutron star binaries have been performed during the last decades, and the emitted gravitational wave profiles and the interior structure of the generated remnants have been analysed in detail. The consequences of a potential appearance of a hadron-quark phase transition in the interior region of the produced hypermassive neutron star and the evolution of its underlying matter in the phase diagram of quantum cromo dynamics will be in the focus of this article. It will be shown that the different density/temperature regions of the equation of state can be severely constrained by a measurement of the spectral properties of the emitted post-merger gravitational wave signal from a future binary compact star merger event.
Post-transcriptional gene regulation through microRNA (miRNA) has emerged as a major control mechanism of multiple biological processes, including development and function of T cells. T cells are vital components of the immune system, with conventional T cells playing a central role in adaptive immunity and unconventional T cells having additional functions reminiscent of both innate and adaptive immunity, such as involvement in stress responses and tissue homeostasis. Unconventional T cells encompass cells expressing semi-invariant T cell receptors (TCRs), such as invariant Natural Killer T (iNKT) and Mucosal-Associated Invariant T (MAIT) cells. Additionally, some T cells with diverse TCR repertoires, including γδT cells, intraepithelial lymphocytes (IEL) and regulatory T (Treg) cells, share some functional and/or developmental features with their semi-invariant unconventional counterparts. Unconventional T cells are particularly sensitive to disruption of miRNA function, both globally and on the individual miRNA level. Here, we review the role of miRNA in the development and function of unconventional T cells from an iNKT-centric point of view. The function of single miRNAs can provide important insights into shared and individual pathways for the formation of different unconventional T cell subsets.
A hypothesis regarding the development of imitation learning is presented that is rooted in intrinsic motivations. It is derived from a recently proposed form of intrinsically motivated learning (IML) for efficient coding in active perception, wherein an agent learns to perform actions with its sense organs to facilitate efficient encoding of the sensory data. To this end, actions of the sense organs that improve the encoding of the sensory data trigger an internally generated reinforcement signal. Here it is argued that the same IML mechanism might also support the development of imitation when general actions beyond those of the sense organs are considered: The learner first observes a tutor performing a behavior and learns a model of the the behavior's sensory consequences. The learner then acts itself and receives an internally generated reinforcement signal reflecting how well the sensory consequences of its own behavior are encoded by the sensory model. Actions that are more similar to those of the tutor will lead to sensory signals that are easier to encode and produce a higher reinforcement signal. Through this, the learner's behavior is progressively tuned to make the sensory consequences of its actions match the learned sensory model. I discuss this mechanism in the context of human language acquisition and bird song learning where similar ideas have been proposed. The suggested mechanism also offers an account for the development of mirror neurons and makes a number of predictions. Overall, it establishes a connection between principles of efficient coding, intrinsic motivations and imitation.
Multidomain enzymes, such as fatty acid synthases (FASs) or polyketide synthases (PKSs), play a crucial role in the biosynthesis of important natural products. They have a high significance in the development of new pharmaceuticals and various research approaches focus on the engineering of these proteins. For example, human type I FAS is an interesting therapeutic target. Owing to its importance in lipogenesis, upregulation of human type I FAS expression has been observed in numerous cancers. Type I FAS is also regarded as important target in antiobesity treatment. Both multidomain enzyme classes - FASs and PKSs - show high structural and functional similarities. Particularly animal type I FAS is most relevant as evolutionary precursor of the PKS family. Therefore, the well characterized FASs are suitable model proteins for the poorly characterized PKSs, to gain deeper understanding in these megasynthases.
Furthermore, fatty acids are considered to be strategically important platform chemicals accessible through sustainable microbial approaches. The recently acquired structural information on FASs provides an excellent understanding of the molecular basis of fatty acid synthesis. The specific understanding of chain-length control, the characterization of a multitude of substrate-specific thioesterases, and the emerging tools and means for metabolic engineering have fostered targeted approaches for modulating chain length. There is large interest in short-chain fatty acids, since these compounds are biotechnologically valuable platform chemicals and biofuel precursors, and attempts on the synthesis of short-chain fatty acids have been reported during the last years.
Primary focus of this thesis lies on the animal type I FASs, which exhibit large conformational variety, as seen in electron microscopy and high-speed atomic force microscopy. Conformational dynamics facilitate productive protein-protein interactions between catalytic domains within the enzyme and aid acyl carrier protein (ACP)-mediated substrate shuttling during the catalytic cycle of fatty acid biosynthesis. To gain deeper insight into the fundamental processes of ACP-mediated substrate shuttling and the underlying conformational dynamics, spectroscopic methods like Förster resonance energy transfer and electron paramagnetic resonance spectroscopy shall be employed. These spectroscopic methods demand site-specific labeling of proteins with fluorophore or spin labels, which can be accomplished with the amber codon suppression technology. Through amber codon suppression, a non-canonical amino acid (ncAA) with an orthogonal functional group is incorporated site-specifically into the protein sequence, which can be used in chemoselective reactions for protein labeling.
This thesis is at the forefront of employing the technology of amber codon suppression for addressing complex biological questions on megasynthases. The successful production of ncAA-modified FASs is challenging. With the aim of incorporating ncAAs into the multidomain 540 kDa large murine FAS, we by far exceed boundaries of documented application of amber codon suppression. Most of the proteins that are reported by Liu & Schultz in applications of amber codon suppression are in the range of 30kDa - for example the TE domain of human FAS. In the same review, the largest protein amber codon suppression was applied to is a potassium channel with roughly 80 kDa. Thus, to the best of my knowledge no protein exceeding 100 kDa has been used in amber codon suppression so far.
In this thesis a low-complex, well-plate based reporter assay is presented, based on an ACP-GFP fusion protein for fast and efficient screening of ncAA incorporation. Reliability and applicability of the reporter assay is demonstrated by successful upscaling to larger protein constructs and increased expression scale.
As outlined in this thesis, we have carefully set up methods for the modification of murine FAS and made several achievements:
(i) We have created our own toolbox with a multitude of suppressor plasmids and various orthogonal pairs. pACU and pACE plasmids are compatible for fast exchange of cassettes, and cloning procedures are optimized for modification of synthetases by site-directed mutagenesis. (ii) We have organic synthesis of several ncAAs stably running in the lab and synthesis of other ncAAs can be established when required. Therefore, extensive screening at moderate costs is possible. (iii) We have established a reporter assay for screening our own library of vectors for amber codon suppression and for optimizing incorporation of ncAAs. (iv) We successfully incorporated ncAAs into subconstructs and full-length murine FAS, and collected initial promising results for the application of these proteins in spectroscopic methods. Thus, laying the foundation for future studies to address fundamental questions of the ACP-mediated substrate shuttling and other conformational dynamics of these enzymes.
Paramyxo- and pneumoviruses include many pathogens with great relevance for human and animal health. To identify common host factors involved in the Paramyxo- and Pneumoviridae life cycle as a basis for new insights in the biology of these viruses and the development of rationally designed therapeutics, genome scale siRNA screens with wild-type measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, were performed. A comparative bioinformatics analysis yielded different members of the coatomer complex I, the translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. The strongest common hit, ABCE1, an ATP-binding cassette transporter member, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for both virus families. While viral protein kinetics showed that ABCE1 knockdown resulted in a drastic decrease of MeV protein expression, viral mRNA kinetics are not directly affected by a reduction of ABCE1.
The impact of ABCE1 on viral and global cellular translation was investigated using both 35S metabolic labelling and non radioactive fluorescent protein labelling. ABCE1 knockdown strongly inhibited the production of MeV proteins, while only modestly affecting global cellular protein synthesis and showed that ABCE1 is specifically required for efficient viral, but not general cellular, protein synthesis, indicating that paramyxoand pneumoviral mRNAs may exploit specific translation mechanisms.
In a second approach the efficacy of the small-molecule polymerase inhibitor ERDRP-0519 against MeV was assessed in squirrel monkeys. Animals treated with the drug experienced less severe clinical disease compared to untreated controls, and this effect correlated with the onset of drug treatment.
We observed a reduction of levels of PBMC-associated viremia and virus release in the upper airways, illustrating effective inhibition of virus replication by the drug treatment. ERDRP-0519 drug treatment also alleviated MeV-induced immunosuppression. In addition to providing proof-of-concept for the support of MeV eradication efforts by preventing disease and transmission with a small-molecule polymerase inhibitor, this dissertation provides a novel perspective on cellular proteins that impact the replication of MeV, MuV and HRSV and highlights the role of ABCE1 as host factor that is required for efficient paramyxo- and pneumovirus translation.