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Long-read 16S amplicon analyses and improved cultivation techniques as joined approach for the identification of viable bacterial populations in silage
Get PDFAims: Lactic acid bacteria (LAB) are crucial for the quality and preservation of silage. Exploration and isolation of the key microbiome are important for improving fermentation processes. While cultivation-dependent methods enable the isolation of LAB, they often overlook organisms with challenging cultivation requirements. Next-generation sequencing provides cultivation-independent microbiome insights. In contrast to commonly used methods, long-read sequencing platforms like the Pacific Biosciences (PacBio) single-molecule real-time (SMRT) platform offer species-level resolution. This study aims to investigate the benefits of a combined cultivation-dependent and -independent approach for silage microbiome analyses. Methods and results: The common isolation medium for LAB was supplemented with sterile pressed juice from plant material improving the cultivation conditions. PacBio amplicon sequencing provided an almost complete and cultivation-independent picture of the bacterial community. The use of mock communities and a live/dead discriminating treatment of the samples revealed that the analysis can be misleading if appropriate controls are not performed. Conclusion: Growth of plant-associated microorganisms can be supported by a plant juice containing isolation medium, allowing isolation of the dominant LAB from silage. Microbial dynamics can be represented using long-read sequencing. However, the use of controls such as a live/dead discrimination and mock communities is essential for the reliability of the data
Quantitative and qualitative tremor evaluation after MR-guided focused ultrasound thalamotomy
Get PDFIntroduction: Tremor syndromes are common neurological disorders, usually distinguished by clinical examination. Ordinal rating scales are widely used to rate tremor severity but are limited by subjective observation, interrater reliability, ceiling effects and lack of knowledge about sensitivity to change emphasizing the relevance of quantitative methods. Methods: To assess tremor characteristics in essential tremor (ET) and Parkinson’s disease tremor (PT) quantitatively, we used a wearable triaxial accelerometer in comparison to a common clinical rating scale. Furthermore, different activation conditions and changes after treatment with MR-guided focused ultrasound (MRgFUS) were examined concomitantly. Patients with disabling, medication-refractory ET (n = 35) or PT (n = 21) undergoing unilateral MRgFUS thalamotomy were assessed before, 1, 6 and 12 months after MRgFUS treatment. Clinical assessments included the Clinical Rating Scale for Tremor (CRST) and accelerometric recordings at rest, posture and kinetic movement. Peak frequencies (fp), frequency width at half maximum (FWHM), tremor stability index (TSI), and half-width power (HWP) were extracted from the power spectrum of acceleration and compared to the CRST. Results: We observed moderate to strong correlations between CRST subscores and log-transformed HWP, whereas significant correlations were only evident in ET when groups were evaluated separately. Fp, FWHM and TSI showed no differences between groups and conditions. Further, repeated measurements after MRgFUS treatment revealed significant changes of tremor severity in both, clinical rating and accelerometric recordings. Discussion: Tremor assessment using accelerometric recordings provided a fast and investigator independent method for tremor characterization and quantitative assessment, which were sensitive to changes after therapeutic interventions
Digital Religion in the Public Sphere : Tehreek-e-Labbaik Pakistan (TLP) and Alternative for Germany (AfD)
Get PDFWhile digital religion and digital protest can ideally serve the common good, religious nationalist and fundamentalist movements have exploited these tools to disrupt the social fabric and create dangerous political outcomes. This paper examines how religious communicators within Tehreek-e-Labbaik Pakistan (TLP) and Alternative for Germany (AfD) perceive and enact their responsibility within digital spaces, leveraging the power of "networked communities" and the collective identity of the digital "crowd" to advance their agendas of religious fundamentalism and political conservatism. Bypassing traditional media, groups like the AfD and TLP exploit digital religion to build communities, spread propaganda that merges religion with national identity, frame political issues as religious mandates, and mobilize collective action. Campbell's concept of the "networked community" demonstrates how digital technologies form decentralized, fluid, and global religious communities, distinct from traditional, geographically bound ones. Both the TLP and AfD have tapped into this new digital religious space, shaping and mobilizing political and religious identities across virtual borders. Gerbaudo's idea of the "digital crowd" complements this by examining how collective action in the digital age reshapes mass mobilization, with social media transforming how political movements operate in the 21st century. Although the AfD's platform is not overtly religious, the party strategically invokes ethno-Christian identity, framing opposition to Islam and Muslim immigration as a defense of German cultural and Christian values. Similarly, the TLP promotes religious nationalism by advocating for Pakistan's Islamic identity against secularism and liberalism and calling for strict enforcement of blasphemy laws. Recognizing digital spaces as tools co-opted by religious nationalist movements, this paper explores how communicators in these movements understand their responsibility for the social and long term consequences of their messages. Using Luhmann's systems theory—where communication is central to social systems—this paper analyzes how the TLP and AfD leverage individuals' need for purpose and belonging to mobilize them digitally. By crafting emotionally charged experiences, these movements extend their influence beyond virtual spaces and into the broader public sphere. Finally, this paper will reflect on the theological implications of these dynamics both on and offline. How do religious communicators in digital spaces reconcile their theological frameworks with the social impact of their communication? Can digital religious communities be harnessed to foster social cohesion and inclusivity instead of exacerbating social divisions? Through this lens, the paper seeks to deepen our understanding of the intersection between digital religion, political mobilization, and theological responsibility in the digital age
Data-Driven Strategies in Neurodegenerative Diseases: Advancing Drug Development and Disease Management
Get PDFNeurodegenerative Disorders, including Alzheimer's, Parkinson's, and Huntington's Disease, pose major challenges to modern medicine due to their progressive nature and impact on patients and the healthcare system. These disorders lead to declines in cognitive, motor, and functional capabilities due to gradual neuron degeneration. Despite extensive research, effective disease-modifying therapies remain elusive, hindered by the complexity of identifying suitable therapeutic targets and the heterogeneity of each condition.
This thesis addresses critical challenges within the pharmaceutical value chain using data-driven methodologies, including machine learning and artificial intelligence, to develop innovative strategies for personalized medical treatments and improved disease management. A key challenge lies in identifying appropriate target structures for active substances. A systems biology approach leverages advanced data analytics for an in-depth analysis of complex interactions within biological pathways, enhancing the understanding of disease mechanisms and guiding the search for effective treatments. Furthermore, determining the appropriate timing and patient selection for treatment is essential. The heterogeneity of symptom progression in Huntington's Disease is examined, identifying two distinct progression subtypes with significant cognitive performance differences. These findings underscore the need for personalized treatment strategies based on individual progression patterns and the importance of recognizing symptom diversity that influences clinical outcomes. Additionally, objective measurements are investigated by evaluating gait sensor data for monitoring symptoms and their progression in Parkinson's Disease. The feasibility of using sensor-based digital gait data as endpoints in clinical trials is assessed by determining necessary sample sizes and measurement effectiveness. This approach aims to establish a reliable framework for integrating health technologies into clinical practice, enhancing patient monitoring and outcomes.
In conclusion, the results of this thesis underscore the potential of data-driven methods in developing disease-modifying treatments for neurodegenerative diseases. Insights gained contribute to understanding potential drug targets, disease progression heterogeneity, and the utility of digital sensors for monitoring, paving the way for more effective drug development and personalized disease management
UAV-based Imaging of Multispectral Reflectance and Solar-Induced Chlorophyll Fluorescence for Crop Monitoring
No full textThe agri-food sector is facing significant challenges due to climate change, unpredictable weather, and rapid population growth. The growing demand to embrace advanced agricultural systems that boost productivity while mitigating climate impacts requires accurate and reliable crop monitoring techniques. In this context, site-specific farm management and remote sensing have become indispensable. Remote sensing offers real-time information about crop growth and health throughout the growing season at different scales. UAV-based remote sensing, in particular, offers a cost-effective tool for monitoring crop growth and health with high spatiotemporal resolution that enables response to field-scale issues by driving informed decision-making. Our study contributes to this evolving landscape by exploring the potential of UAV-based multispectral imaging in crop monitoring on the field scale.
In the first study, high-resolution imagery from the DJI Phantom 4 multispectral UAV system was employed to monitor the seasonal development of spelt in a biochar-enriched experiment. A straightforward data processing workflow was developed based on an empirical line method to convert raw UAV data to normalized and comparable reflectance maps and calculate various vegetation indices. Results indicated that EVI was the most effective index in relation to the actual yield, indicating better spelt development over the biochar-enriched plots with a full conventional fertilization amount compared to controls that received the same conventional fertilization.
The second study addressed the retrieval of sun-induced fluorescence, F760, from SIFcam, a dual-camera system prototype mounted on a UAV. A comprehensive overview and advancements of the developed methodology for SIFcam imagery, in addition to a second innovative workflow, were presented. The F760 retrieved from the two workflows showed strong correlations with ground-based measurements (R² = 0.92) and moderate correlations with airborne imaging spectrometer HyPlant (R² = 0.56, 0.52 for workflows 1 and 2b, respectively). The SIFcam has shown its capability to effectively disentangle the fluorescence signal from canopy reflectance with a moderate level of accuracy and adequate stability in data collection at the field scale, with less than one-pixel variation between spectral channels in both horizontal and vertical directions.
The third study investigated the potential of integrating SIFcam F760 alongside UAV-based multispectral VIs to characterize and delineate diverse new and old winter wheat cultivars. SIFcam demonstrated a notable potential in capturing the variability of F760 between wheat cultivars with structural and pigment differences. New wheat cultivars generally revealed higher F760, consistent with their higher chlorophyll content, yet old cultivar Banco indicated that canopy architecture could significantly modulate TOC F760, with F760 values comparable to or even exceeding those of certain new cultivars. VIs sensitive to chlorophyll content, particularly TCARI/OSAVI (Cohen's d >= 0.5), outperformed structure-related VIs and F760 for distinguishing the cultivars. SIFcam proved to be a valuable tool for field plant phenotyping and potentially guiding breeding programs
Total synthesis of Epicoccolide A & B and two related analogs
Get PDFThe family of epicoccolides has been known for over a decade now and show remarkable biological properties in a variety of fields. Different groups have reported antibacterial, antifungal and antitumor reactivity. More recently, an inhibition of galactosylceramide sulfotransferase by epicoccolide B was patented. This sulfotransferase is involved in the very rare but deadly disease metachromatic leukodystrophy. To be able to use the mentioned biological activities it is essential to gain access to large amounts of the desired natural product. Extraction from nature is a costly and time-consuming venture and no reliable source for the required material. To provide a solution for this problem a successful total synthesis of the natural products epicoccolide A and epicoccolide B was the goal of this thesis.
Efforts into the total synthesis of epicoccolide B have been invested by previous members of our working group and were continued. The first total synthesis of epicoccolide B was achieved after investigating several different routes with varying outcomes and a multitude of challenges that needed to be overcome. In the course of these investigations two structural analogs were synthesized as well.
After the final step of the total synthesis epicoccolide B showed interesting and unprecedented reactivity under mild aqueous conditions. The outcome and reproducibility of this reaction was examined in detail leading to the first total synthesis of epicoccolide A. Comparison of synthetic epicoccolide A to reported literature resulted in structural reassignment and questioning of the previously proposed biosynthetic pathways. To clear up these problems, plausible answers have been provided including a newly proposed biosynthesis.
First attempts at the total synthesis of epicocconigrone A were also initiated but exceeded the final scope of this thesis. The project was handed off to a new member of our working group with the current plans presented herein. Finally, initial testing of the bioactivity of the two structural analogs synthesized during the course of this project revealed valuable data that is worthwhile to be pursued further
On the Bäcklund transform and the stability of the line soliton of the KP-II equation on the plane
Get PDFWe provide a detailed study of the Bäcklund transform (or soliton addition map) of the KP-II equation on the Euclidean plane at critical regularity. The transform has the effect of superimposing a modulated line soliton onto a given KP-II solution. Our analysis is motivated by the problem of stability of KP-II multisolitons in L2(ℝ2), currently solved only for the single soliton, and by the broader question of understanding the connections between integrability and soliton stability in PDEs admitting line solitons.
We show that the transform is well-defined in a critical Sobolev space, establish appropriate L2 estimates, and prove that it commutes with the KP-II flow. The mapping properties of the transform are more complicated than those of KdV and other 1D models. In this direction, we show that its range, when intersected with a small ball in a mildly weighted space, forms exactly a codimension-1 manifold. This codimension-1 condition is an intrinsic property of the Bäcklund transform, and we conjecture that it corresponds to a known long time behavior of perturbed line solitons.
The L2-stability of the line soliton in the aforementioned manifold follows as an immediate corollary, providing a first partial stability result at sharp regularity. Using this map for the full stability of solitons will require a follow-up study.
Finally, we show the construction of a multisoliton addition map for a certain class of KP-II multisolitons
Renal tissue-resident macrophages promote cystogenesis in early polycystic kidney disease
Get PDFAutosomal-dominant polycystic kidney disease (ADPKD) is a ciliopathy characterized bymutations in PKD1 or PKD2, which drive cystogenesis in renal epithelial cells. Immune cells, particularly macrophages, contribute to disease progression, yet their role remains incompletely understood. Here, we performed an in-depth analysis of renal macrophage ontogeny and phenotype and investigated their function in an ADPKD mouse model (Pkd1RC/RC) with adult onset and slow disease progression. We demonstrate that the numbers of tissue-resident macrophages were already increased before cyst formation. Using a flow cytometry screening panel, we further characterized the tissue-resident macrophage populations using surface markers and identified a novel marker that shows the potential to determine macrophage remodeling at different disease stages. To reveal the cellular interaction of tissue-resident macrophages and renal epithelial cells in further detail, we established a 3D co-culture system, demonstrating that tissue-resident macrophages from Pkd1RC/RC mice, isolated at a stage before cysts were observed, already showed enhanced cystogenesis in vitro. These findings underscore the crucial role of tissue-resident macrophages in ADPKD and suggest targeting epithelial cell–macrophage interactions as a promising therapeutic avenue
Ingestion of micro- and nanoplastic perturbs tissue homeostasis and macrophage core functions
Get PDFPlastic pollution has emerged as a global environmental crisis of unprecedented scale. Micro- and nanoplastic (MNP) pervade ecosystems, resulting in persistent exposure for all living organisms, including humans. MNP have been detected in human blood. Additionally, animal studies indicate MNP ability to cross biological barriers and accumulate in organs such as the liver, spleen, and brain. Nevertheless, the impact of plastic accumulation on tissue homeostasis and immune cell function remains poorly understood. This study investigates the consequences of chronic polystyrene particle ingestion using a mouse model.
Following oral ingestion, MNP breach tissue barriers and accumulate in multiple organs. Hepatic and splenic macrophages are pivotal in the uptake and retention of MNP, leading to their long-term persistence in these tissues. This prolonged presence disrupts metabolic homeostasis in the liver and adipose tissues without inducing systemic inflammation. Moreover, MNP ingestion exacerbates metabolic dysregulation under additional stress, such as a high-fat diet, worsening glucose intolerance.
On a cellular level, MNP accumulation in Kupffer cells, the liver-resident macrophages, impairs their phagocytic function, reducing their ability to clear circulating bacteria. Additionally, MNP-exposed mice exhibit signs of an autoimmune phenotype.
Altogether, our results demonstrate the hazardous nature of MNP ingestion on tissue homeostasis, metabolism, and macrophage functionality. These findings suggest that chronic exposure to plastic particles could contribute to the rising prevalence of environmentally linked metabolic and autoimmune diseases
Electrophysiological Indicators of Selective Attention to Affect
Get PDFFor several decades, the interplay between attention and emotion has attracted significant interest in the fields of neuroscience and psychology. While much is known about the ability of emotional content to involuntarily capture human attention, less research has focused on the voluntarily directed attention to (the valence of) specific emotional stimuli. In order to better understand the underlying neural mechanisms of this highly dynamic process, researchers frequently rely upon event-related potentials (ERPs), which allow the separation of distinct temporal processing stages. The few studies on this specific topic have demonstrated that emotional stimuli benefit from selective attention to valence primarily during late, controlled processing. However, recent work has suggested that selective attention may also modulate emotional processing during early, perceptual stages. The present dissertation therefore aimed to clarify the nature of this previously observed effect and to generalize the observations to other types of emotional stimuli.
To this end, a series of four ERP studies was conducted using an experimental task in which attention was selectively directed toward one particular valence (e.g., positive). In Study I, the influence of lexical word properties on the early processing of selectively attended emotional words was investigated. In Study II, the neural processing of emotional words whose valence had not been selectively attended was explored in greater detail and integrated into theories on affective information processing. In Study III, emotional faces were used as stimuli in order to examine potential differences in neural processing during the selective attention to affect compared to words and pictures. In Study IV, the influence of participant gender and face gender on the processing of emotional faces whose expression was selectively attended was explored.
The combined findings demonstrate that selective attention to affect partially elicits analogous neural processing for emotional words and faces, while also revealing notable differences between the two stimulus categories. Most importantly, it was confirmed that the perceptual processing of emotional stimuli at very early stages can be modulated by selective attention. While this effect appeared to be more pervasive for words, a particularly interesting pattern was also identified for faces under specific conditions. On the other hand, subsequent holistic visual stimulus processing was characterized by attention-independent processing of the emotional content. At mid-latency ERPs, there was moderate evidence for an attention-sensitive enhancement of emotional face processing, presumably indicative of the special role of emotional faces in human social life. Finally, the largest effects of task-related attention as well as a sustained attentional bias toward unattended negative stimuli manifested during late processing stages. As a whole, this work extends previous research and provides valuable insights into the electrophysiological signatures of top-down selective attention to affect and its interaction with the bottom-up processing of emotional stimuli.Das Zusammenspiel von Aufmerksamkeit und Emotion ist seit mehreren Jahrzehnten ein zentrales Forschungsfeld der Neurowissenschaften und der Psychologie. Während bereits umfangreiche Erkenntnisse über die Fähigkeit emotionaler Inhalte, die menschliche Aufmerksamkeit unwillentlich auf sich zu ziehen, vorliegen, wurde die willentliche Steuerung der Aufmerksamkeit auf bestimmte emotionale Stimuli (und deren Valenz) vergleichsweise spärlich erforscht. Um die neuronalen Mechanismen dieses hochdynamischen Prozesses besser zu verstehen, stützt sich die Forschung dabei häufig auf ereigniskorrelierte Potenziale (ERPs). Diese ermöglichen eine Differenzierung zwischen verschiedenen zeitlichen Verarbeitungsphasen. Die wenigen Studien zu diesem spezifischen Thema haben gezeigt, dass emotionale Reize von der selektiven Aufmerksamkeit auf ihre Valenz vor allem während der späten, kontrollierten Verarbeitungsphasen profitieren. Neuere Forschung legt jedoch nahe, dass selektive Aufmerksamkeit auch die emotionale Verarbeitung während der frühen, perzeptuellen Phasen modulieren kann. Die vorliegende Dissertation hatte daher zum Ziel, die Wirkungsmechanismen dieses zuvor beschriebenen Effekts zu beleuchten und die Beobachtungen auf andere Formen emotionaler Reize zu verallgemeinern.
Zu diesem Zweck wurden vier ERP-Studien mit einer experimentellen Aufgabe durchgeführt, bei der die Aufmerksamkeit selektiv auf eine bestimmte Valenz (z. B., positiv) gerichtet wurde. In Studie I wurde der Einfluss lexikalischer Worteigenschaften auf die frühe Verarbeitung von selektiv beachteten emotionalen Wörtern erforscht. In Studie II wurde die neuronale Verarbeitung von emotionalen Wörtern, deren Valenz nicht selektiv beachtet wurde, genauer untersucht und im Rahmen von Theorien zur affektiven Informationsverarbeitung betrachtet. In Studie III wurden emotionale Gesichter als Reize verwendet, um mögliche Unterschiede in der neuronalen Verarbeitung während der selektiven Aufmerksamkeit auf Affekt im Vergleich zu Wörtern und Bildern zu untersuchen. In Studie IV wurde getestet, welchen Einfluss das Geschlecht der Versuchspersonen und des präsentierten Gesichts auf die Verarbeitung von emotionalen Gesichtern, deren Ausdruck selektiv beachtet wurde, hat.
Die zusammengefassten Ergebnisse legen nahe, dass selektive Aufmerksamkeit auf den Affekt eine zumindest in Teilen ähnliche neuronale Verarbeitung für emotionale Wörter und Gesichter auslöst, wobei aber auch deutliche Unterschiede zwischen den beiden Stimuluskategorien zu erkennen sind. Insbesondere wurde dabei bestätigt, dass die perzeptuelle Verarbeitung emotionaler Reize in sehr frühen Stadien durch selektive Aufmerksamkeit moduliert werden kann. Hier zeigte sich, dass dieser Effekt bei Wörtern ausgeprägter zu sein scheint, auch wenn bei Gesichtern unter bestimmten Bedingungen ebenfalls ein besonders interessantes Muster beobachtet werden konnte. Im Gegensatz dazu war die anschließende holistische visuelle Stimulusverarbeitung durch eine aufmerksamkeitsunabhängige Verarbeitung des emotionalen Inhalts gekennzeichnet. Hinsichtlich der ERPs mit mittlerer Latenz fanden sich moderate Hinweise auf eine aufmerksamkeitsabhängige Verstärkung der Verarbeitung emotionaler Gesichter, was die besondere Relevanz emotionaler Gesichter im menschlichen Sozialleben betont. In den späten Verarbeitungsphasen zeigten sich schließlich die größten Effekte der aufgabenbezogenen Aufmerksamkeit sowie eine anhaltende Verschiebung der Aufmerksamkeit in Richtung unbeachteter negativer Reize. Zusammenfassend erweitert diese Dissertation frühere Forschungsarbeiten und liefert wertvolle Einblicke in die elektrophysiologischen Signaturen, die die selektive Top-down-Aufmerksamkeit für Affekt und ihre Interaktion mit der Bottom-up-Verarbeitung emotionaler Stimuli abbilden