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Hidden in plain sight
Get PDFStudies have shown that in reality, we are drastically underestimating species numbers and that a large proportion of the global diversity is still awaiting discovery or description (Engel et al., 2021; González-Oreja, 2008). Yet the bulk of the planet’s hidden diversity (and biomass) is found in groups that are difficult to study and have therefore received very little taxonomic attention in the past (so-called “dark taxa”) (Hardulak, 2020; Hartop et al., 2022; Hausmann et al., 2020; Meier et al., 2021; Morinière et al., 2019). These groups are so hyperdiverse, that dark taxa have also been referred to as “open-ended” taxa because species number estimates are almost impossible to make (Hartop et al., 2022). The majority of dark taxa are found among two insect orders, Diptera (flies) and Hymenoptera (ants, bees, wasps), and consist in large part of non-brachyceran Diptera such as midges and gnats, as well as parasitoid wasps (Hausmann et al., 2020). Being cryptic diverse, highly abundant, and miniscule (<2 mm), the analysis of these groups is very demanding so often, they are simply cast aside and analysis is limited to better studied and easier-to-handle taxa. At the same time, the fact that dark taxa are so abundant in samples (they can make up more than 70% of specimen numbers) implies that they play an essential in ecological functioning (GBOL III, 2023). Conversely, this means that it is all the more important to make these groups tangible to research so that they can be implemented into conservation measures.
If we want to study and describe species more effectively, we need a taxonomic renaissance in descriptive taxonomy (Giangrande, 2003). Morphological methods, which have been used for the last 250 years, alone do not provide sufficient discriminatory information for the tiny, cryptic diverse species of dark taxa. Luckily, recent advances in molecular biology are providing the much-needed means to accelerate species discovery by providing DNA-based discrimination methods (Morinière et al., 2016; Wang et al., 2018). These not only drastically speed-up sample processing and species identifications, these also enable the analysis of entire insect communities in one go (Srivathsan et al., 2015). Also, ever more scientists are recommending the use of integrative workflows which implement methods from different disciplines for species description and delimitation (Meier et al., 2022). Using such complementary approaches increase scientific vigor, as no single method is error-free (Dayrat, 2005; Schlick-Steiner et al., 2010).
The main goal of this thesis is to develop an integrative framework for the rapid processing of large samples of dark taxa with three specific objectives. These are (1) identifying the dark diversity in temperate regions, (2) developing an integrative methodology to assess samples of dark taxa, and (3) testing the usability of preservative ethanol of insect bulk samples for metabarcoding applications.
The first objective aims at raising awareness for the presence of dark taxa not only in a tropical, but also in a temperate setting (Publications I-III). Data obtained through large-scale DNA barcoding on Malaise trap samples from Padang, Sumatra (2016) and from Germany (2012-2017) were analyzed. The large prevalence of dark taxa in Malaise trap samples (in terms of species diversity and specimen abundance) was demonstrated, and species numbers for four dipteran dark taxa were extrapolated to provide data-based species estimates for Germany.
Second, having raised awareness regarding the hidden diversity of dark taxa in temperate regions, a strategy is formulated for tackling one dark taxon from large samples (Publication IV). Using Chironomidae (non-biting midges; Diptera, Nematocera) as a model group, an integrative approach was proposed which includes (i) a three-level subsampling method to reduce the workload of sample processing, (ii) morphology- and (iii) DNA-based methods in parallel to evaluate species diversity, and (iv) examining possible inconsistencies across methods. Here, the results show that with this integrative framework, more than 90% of all species were detected despite having identified only 7% of individuals. Also, the results demonstrate that using either identification method on its own would have been prone to errors that would have gone undetected.
Lastly, the usability of ethanol-based DNA for metabarcoding applications is assessed (Publication V). Here, the research question is whether ecological information is conserved in the DNA that is extracted from the collection fluid of bulk samples. If so, this would imply that the usual step of specimen homogenization for DNA extraction can be bypassed because the ethanol of samples can be simply poured out and used for analysis instead. In this manner, all specimens are left intact for further analyzes. Here, the results suggest that ethanol-based DNA does not conserve ecological information and until future research has provided more successful results, it is recommended that researchers dealing with terrestrial ecosystems be careful when using ethanol-based DNA.
In conclusion, this thesis builds a framework that combines different disciplines to efficiently study the immense (hidden) insect diversity that is housed in our temperate environments
Charakterisierung von Defekten der Signaltransduktion bei angeborenen Erkrankungen des Immunsystems
Get PDFGeneration and analysis of a gene regulatory network for Chlamydomonas reinhardtii
Get PDFStopping climate change requires renewable energy sources. Microalgae are a promising biotechnological resource for biofuels. Under stress conditions they produce large quantities of storage lipids as triacylglycerides (TAGs), which can be further converted into biodiesel. To optimize the biotechnological production of valuable compounds such as TAGs in microalgae, a thorough system-level understanding of the underlying regulatory mechanisms is required.
Current knowledge is based on mutant screens, co-expression analyses, and predictions but a systems-level perspective is missing. The present work is dedicated to expanding the existing knowledge of fundamental regulatory mechanisms in microalgae and enabling advanced biotechnological use of microalgae.
All regulatory processes in a cell are mediated and controlled by interactions between macromolecules, such as protein-protein interactions (PPI), protein-DNA interactions (PDI), or interactions between proteins and RNA or small molecules.
These interactions are organized in complex networks, and the systematic mapping of these interactomes and regulomes is essential for understanding complex biological relationships in an organism.
In order to enable large-scale mapping of PPIs and PDIs for the model organism of microalgae, Chlamydomonas reinhardtii (C. reinhardtii), a comprehensive set of protein-encoding open-reading frames (ORFs) was generated. This ORFeome allows for an unbiased and high-throughput approach to performing proteomic studies.
The successfully generated ORFeome collection consists of 8,627 Gateway® Entry clones. It enables systematic investigations of fundamental biological and regulatory processes in C. reinhardtii.
PDIs are mediated by transcription factors (TFs) that bind to specific genomic DNA sequences in promoter regions, enhancers, and other cis-regulatory elements, thereby regulating the expression of target genes. These interactions are described in gene regulatory networks (GRN). Using the Yeast-1-hybrid (Y1H) method, the first experimental-based large-scale GRN of C. reinhardtii was constructed, consisting of 1,451 interactions between 142 TFs binding to 200 promoter regions.
To determine the quality of the Y1H network, a second orthogonal assay, called PampDAP-seq, was performed. This modified DAP-seq method identified 320 unique PDIs for six TFs. The comparison of DAP-seq interactions with found Y1H interactions showed an overlap of 23.8 %, which highly supports the Y1H results.
The generated network map was hierarchically structured according to the outdegree of the TFs. 15 TFs represent the highest level in this network and are responsible for 66.7 % of all interactions.
In addition, multiple TFs, including previously known stress-related TFs, were found to form an intermediate level of regulation that combines various signals from other TFs to mediate a subsequent cellular response. Moreover, a distributed regulation structure for metabolic pathway promoters was observed.
84.5 % of metabolic promoters are targeted by more than two TFs.
This indicates that each metabolic pathway is regulated by a large number of TFs, a distinct characteristic of higher plants like Arabidopsis thaliana (A. thaliana).
In addition, four promising key regulators of the C. reinhardtii lipid metabolism were identified.
The successfully generated ORFeome collection provides a resource for the in-depth exploration of fundamental biological processes.
Furthermore, the first experimental-based GRN for any microalgae provides valuable insights into the global structure of transcriptional regulation and can pave the way for advanced biotechnological engineering in microalgae
On simulations of cosmic rays in the large-scale structure of the universe
Get PDFKosmische Strahlung, auch Cosmic Rays (CRs) genannt, in Form von relativistischen Protonen und Elektronen sind die Quelle nicht-thermischer Strahlung in einer Vielzahl astrophysikalischer Systeme. Diese Strahlung gibt Einblicke in die Stärke und Struktur von Magnetfeldern, kosmische Stoßwellen und nicht-thermischer Druckkomponenten im interstellaren oder intergalaktischen Medium.
In der großräumigen Struktur des Universums sind CR Elektronen die Quelle für Synchrotron Emission in Radio Halos, Radio Relikten und den Jets aktiver galaktischer Kerne.
CR Protonen andererseits sollten durch die Interaktion zwischen CR Protonen und den thermischen Protonen des Intra-Cluster Medium diffuse Gamma-Strahlung produzieren. Diese Gamma-Strahlung wurde jedoch bisher nicht beobachtet. Eine Abschätzung dieser Gamma-Strahlung wird benötigt um einen Einblick in die nicht-thermischen Druckkomponenten von Galaxienhaufen zu erhalten und um Observationsfenster für die Beobachtung von Dunkler Materie zu finden.
Simulationen des sogenannten Cosmic Web ermöglichen Einblicke in die Entstehung und Entwicklung der größten gravitativ gebundenen Strukturen des Universums. Sogar die modernsten Simulationen verfügen nicht über die benötigte Auflösung, um kosmische Strahlung aus ersten Prinzipien zu simulieren. Wir benötigen deshalb eine sorgsame Beschreibung für die Physik komischer Strahlung, die sich unter der Auflösungsgrenze dieser Simulationen befindet, um den Effekt der kosmischen Strahlung auf die Strukturbildung unseres Universums zu studieren.
In dieser Arbeit fassen wir die Entwicklung von Crescendo: Cosmic Ray Evolution with SpeCtral Electrons aND prOtons zusammen. Crescendo ist ein numerisches Modell, welches die Spektren von CR Protonen und Elektronen als stückweise Potenzgesetze darstellt und deren zeitliche Entwicklung in Simulationen kosmischer Strukturbildung berechnet. Diese zeitliche Entwicklung berücksichtigt folgende Aspekte: Die Beschleunigung kosmischer Strahlung an Stoßwellen, hervorgerufen durch Kollisionen massiver Galaxienhaufen und Massenakkretion, oder Supernova Explosionen, Energieänderungen durch adiabatische Expansion oder Kompression des umliegenden Gases, Energieverluste durch Synchrotron-, inverse Compton Strahlung und Teilchenkollisionen, Energiezunahme durch turbulente Nachbeschleunigung, sowie Transport von CR Teilchen durch Advektion und Diffusion. Die zeitliche Entwicklung der Spektren erlaubt es uns Observablen wie Synchrotron Emission und die Emission von Gamma-Strahlung selbstkonsistent
zu berechnen und mit realen Beobachtungen zu vergleichen.
Nach einer allgemeinen Einleitung in Teil I stellen wir in Teil II das Modell vor und vergleichen die Genauigkeit mit analytischen Lösungen. In den Kapiteln von Teil III zeigen wir die Anwendung auf die Simulation verschiedener kosmischer Strukturen mit zunehmender Komplexität.
Zuerst wenden wir Crescendo auf idealisierte Simulationen kollidierender Galaxienhaufen an.
Das erlaubt es uns die Beschleunigung von kosmischer Strahlung an den resultierenden Stoßwellen und deren Auswirkung auf die Entwicklung von Radio Relikten zu untersuchen. Wir sind in der Lage grundlegende Beobachtungen zu reproduzieren, wie beispielsweise die Form des Synchrotron Spektrums oder die Versteilerung der Synchrotron Spektren hinter den Stoßwellen.
Im darauffolgenden Kapitel untersuchen wir die Wechselwirkung zwischen kollidierenden Stoßwellen und deren Einfluss auf die Beschleunigung kosmischer Strahlung in einer ultrahoch aufgelösten zoom-in Simulation eines massiven Galaxienhaufens. Das erlaubt es uns eine Erklärung für die Entstehung einer neu entdeckten Klasse von Radio Relikten zu finden, der sogenannten "Wrong Way Radio Relics". Diese Relikte zeigen komplexe Morphologie, wobei das Relikt zum Zentrum des Galaxienhaufens hingebeugt ist, anstatt die typische Beugung weg vom Zentrum des Haufens aufzuweisen. Mit unserem Modell sind wir in der Lage zu zeigen, dass diese Relikte entstehen können, wenn eine sich nach Außen bewegende Stoßwelle von einer einfallenden Galaxiengruppe deformiert wird.
In den zwei darauffolgenden Kapiteln wenden wir unser Modell in einer Simulation eines kosmologischenVolumens an, um diffuse nicht-thermische Strahlung im CosmicWeb vorherzusagen.
Wir konzentrieren uns dabei zuerst auf die Synchrotron Strahlung relativistischer Elektronen indem wir Crescendo auf eine Version des SLOW Simulationssatzes und zoom-in Simulationen des Coma Galaxienhaufen anwenden. Wir finden konsistente Teilchenbeschleunigung an Akkretionsschocks um Galaxienhaufen und Filamente des CosmicWeb, welche signifikante Saat-Populationen von CR Elektronen produziert. Wir untersuchen die daraus resultierende diffuse Synchrotron Strahlung unter Berücksichtigung verschiedener Magnetfeldmodelle und finden diffuse Emission in allen Bereichen des CosmicWeb. Allerdings liegt diese Emission selbst mit den optimistischsten Parametern für Teilchenbeschleunigung und Magnetfeldstärke 1-2 Größenordnungen unter der Sensitivität moderner Radioteleskope.
Zuletzt analysieren wir die CR Protonen derselben Simulation, um Vorhersagen für diffuse Gamma-Strahlung in Galaxienhaufen und Filamenten des Cosmic Web zu treffen. Wir finden CR Protonenbeschleunigung und damit diffuse Gamma-Strahlung in allen Bereichen des CosmicWeb. Der beobachtbare Strahlungsfluss liegt 3-4 Größenordnungen unter der derzeitigen oberen Grenze welche mit dem Fermi-LAT Instrument detetktiert werden kann. Wir diskutieren daraufhin die Auswirkungen unserer Parameter für Teilchenbeschleunigung und die Genauigkeit unserer Stoßwellendetektion auf diese Ergebnisse und finden, dass die Auswirkungen signifikant sein können. Deshalb sind zukünftige zoom-in Simulationen nötig, um diese Ergebnisse zu verifizieren.Cosmic rays (CRs) in the shape of relativistic protons and electrons are the source of non-thermal radiation in a plethora of astrophysical systems. Their emission provides insights into the strength and structure of magnetic fields, cosmic shock waves, and non-thermal pressure components in the interstellar or intergalactic medium.
In the large-scale structure of the Universe CR electrons are the likely source of synchrotron emission from Radio Halos, Radio Relics, and AGN jets.
CR protons on the other hand should be detectable via diffuse gamma-rays from their interaction with the thermal background gas, however, this emission has not yet been found. Estimating the gamma-ray emission from this process is required to study the non-thermal pressure support in clusters, as well as finding observational windows for potential detection of Dark Matter interaction.
Simulations of the Large-Scale Structure of the Universe, the so-called Cosmic Web, give insights into the origin and evolution of the largest gravitationally bound structures in the Universe. Even state-of-the-art simulations of cosmological structure formation lack the resolution to simulate the effect cosmic rays have on their environment from first principles. We therefore require a careful sub-grid description of cosmic ray physics that can be included in such simulations to model the effect cosmic rays may have on the evolution of cosmic structure.
In this work, we summarize the development of Crescendo: Cosmic Ray Evolution with SpeCtral Electrons aND prOtons, a cosmic ray model that represents the spectra of cosmic ray protons and electrons as piece-wise power-laws and evolves these spectra in time on-the-fly within simulations of cosmological structure formation. This time evolution accounts for: The acceleration of CRs at shocks caused by collisions between massive galaxy clusters and mass accretion, or supernova explosions, energy changes due to adiabatic compression or expansion of the surrounding gas, energy losses due to synchrotron emission, inverse Compton scattering, and Coulomb collisions, energy gains due to turbulent re-acceleration, and transport of CRs through advection and diffusion. The time evolution of these spectra further allows us to obtain observables such as synchrotron- and gamma-ray emission self-consistently, which can be compared to real observations.
After a general introduction in Part I, we introduce the model and provide tests of its performance against analytic solutions in Part II. In the chapters of Part III, we show its application to a number of simulations of cosmic structures with increasing complexity.
First, we apply Crescendo to simulations of idealized galaxy cluster mergers. This allows us to study CR acceleration at merger shocks and the formation of Radio Relics. We are able to reproduce key observables such as the synchrotron spectrum and the spectral steepening downstream of the relic.
In the subsequent chapter, we study the interaction of colliding shock waves and their impact on CR acceleration in an ultra-high resolution zoom-in simulation of a massive galaxy cluster. This allows us to provide an explanation for the formation of an only recently discovered class of radio relics, referred to as "Wrong Way Radio Relics". These relics show complex morphologies with the relic bent towards the cluster center, instead of the typical bend away from the cluster center.
With our model, we are able to show that these radio relics can form if an in-falling group of galaxies collides with an outwards traveling shock wave and deforms the radio relic as it passes through the shock surface.
In the two following chapters, we extend our modeling to a constrained simulation of a cosmological volume to study diffuse non-thermal emission from the Cosmic Web.
We will first study diffuse synchrotron emission from cosmicweb filaments by applying Crescendo to a realization of the SLOW simulation set and a number of zoom-in simulations of the Coma cluster. We find consistent CR acceleration at accretion shocks onto galaxy clusters and cosmic web filaments, which produce significant CR seed populations. We then investigate the diffuse emission those CR populations can produce under various magnetic field models and with the influence of turbulent re-acceleration of CRs. We find diffuse emission in all regimes, however, even with the most optimistic parameters for magnetic field strength and CR injection this emission still lies 1-2 orders of magnitude below the detection limit of current radio telescopes.
Finally, we analyze the same simulation as in the previous chapter but consider the CR proton population. This allows us to make predictions for diffuse gamma-ray emission in galaxy clusters and cosmic web filaments. We find CR proton acceleration and with that diffuse gamma-ray emission in all regions of the cosmic web. However, the obtained gamma-ray flux lies 3-4 orders of magnitude below the current upper limits obtained with Fermi-LAT. We discuss the impact of CR injection parameters and the performance of our on-the-fly shock finder on these results and find that the impact can be substantial. Future higher-resolution zoom-in simulations will be required to verify these results
Macroeconomic consequences of educational composition: sectoral allocation, inequality, and automation
Get PDFDevelopment of a mCherry-DMDEx23 positive read-out in vitro platform for screening PMO–xenopeptide conjugates
Get PDFSexuelles Risikoverhalten und STI-Prävention bei Jugendlichen und jungen Erwachsenen
Get PDFJugendliche und junge Erwachsene können aufgrund ungeschützter Sexualpraktiken, mangelndem Wissen und eingeschränktem Zugang zu Präventionsmaßnahmen als Hochrisikogruppe für STIs und HIV erklärt werden. Die oftmals geringe Wahrnehmung des eigenen Infektionsrisikos kann auf mangelndes Wissen über Übertragungswege und Schutzmöglichkeiten zurückgeführt werden (22, 36).
In der Vergangenheit haben sich Präventionskampagnen vor allem auf HIV konzentriert, was in begrenztem Wissen von Jugendlichen und jungen Erwachsenen über andere STIs resultierte. Scham, Angst und Stigmatisierung tragen ebenfalls dazu bei, dass die Inanspruchnahme von STI-Tests und Aufklärungsangeboten stagniert. Die PrEP hat sich bei der Senkung der HIV-Prävalenz als wirksames Mittel erwiesen. Allerdings könnte aufgrund einer Fehlinterpretation des eigenen Ansteckungsrisikos eine Zunahme der Übertragung anderer STIs vorliegen (12, 32).
Um die Ausbreitung von HIV und STIs langfristig eindämmen zu können, ist es von entscheidender Bedeutung, die Angst, das Stigma und den Mangel an Wissen unter Jugendlichen und jungen Erwachsenen durch umfassende Aufklärungsprogramme und einen optimierten Zugang zu Test- und Behandlungsmöglichkeiten zu bekämpfen (7, 11).
So kann die angemessene und kontinuierliche Verwendung von Kondomen als eine der wirksamsten Methoden zur Verringerung der Prävalenz von STIs und HIV angesehen werden. Trotz ihrer hohen Wirksamkeit werden Kondome von Jugendlichen und jungen Erwachsenen häufig nicht konsequent genutzt. Spezifische Aufklärungskampagnen und die Förderung des Kondomgebrauchs können daher gezielt beitragen, Jugendliche und junge Erwachsene zu ermutigen, regelmäßig Kondome zu nutzen, um sich vor STIs und HIV zu schützen (36-38).Adolescents and young adults are a high-risk group for STIs, including HIV, due to unprotected sexual practices, lack of knowledge, and limited access to prevention methods. The low perception of one's own risk of infection is partly due to a lack of knowledge about transmission routes and protection options especially condoms (22, 36).
Shame, fear, and stigma also play a role in reducing the uptake of STI testing and education services. PrEP has been effective in reducing the prevalence of HIV, but concerns exist that its widespread use may lead to an increase in the transmission of other STIs. However, available data suggest that the impact of PrEP on STI transmission is limited (12, 32).
Addressing the fear, stigma, and lack of knowledge among adolescents and young adults through comprehensive sex education programs and optimized access to testing and treatment options is critical to curbing the spread of HIV and STIs (7, 11).
In addition, the adequate and continuous use of condoms, can be considered one of the most effective methods for reducing the prevalence of sexually transmitted infections and HIV. Despite their high efficacy, adolescents and young adults often exhibit inconsistent condom use. Targeted education campaigns and promotion of condom use can thus help overcome these barriers and encourage young people to use condoms regularly to protect themselves from STIs and HIV (36-38)
Role of macrophage CB1 in atherosclerosis
Get PDFAlthough the potential connection between the cannabinoid CB1 receptor and atherosclerosis has been suggested, the specific influence it exerts on the various cell types involved in the disease remains unclear. Here, we investigated its role in myeloid cells, which are key cellular effectors in atherosclerosis. Male mice with myeloid-specific knockout of the CB1-encoding gene (Cnr1) on an atherogenic apolipoprotein E (Apoe) deficiency background exhibited notably smaller lesions and necrotic cores compared to the control group. However, in females, only moderate effects were observed, and primarily at an advanced stage of the disease. The atheroprotective effects in male mice were attributed to reduced recruitment of arterial monocytes, decreased proliferation of plaque macrophages, and a less inflammatory polarization state. Interestingly, the sex-specific variances in CB1 signaling within murine macrophages were reproducible in vitro and mitigated by estradiol treatment. Detailed analysis of kinase activity profiling revealed the involvement of p53 signaling and cyclin dependent kinases in mediating the effects of CB1. Unbiased transcriptomic profiling further confirmed the role of CB1 in regulating macrophage oxidative metabolism, which was subsequently validated by metabolic flux assays. Notably, CB1 deficiency or antagonism led to an improvement in oxidative energy metabolism. Additionally, the peripherally acting CB1 antagonist JD5037 halted early plaque formation in male mice. To summarize, impaired CB1 signaling in macrophages reduces their recruitment to arteries, local proliferation, and inflammatory reprogramming, leading to protection against atherosclerosis, especially during the early disease stages. The phenotype was only observed in male mice, which may hint to a sex-specific difference of macrophage CB1 signaling