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Repetition suppression in the auditory cortex : an interdisciplinary investigation
Get PDFAuditory sensory memory is essential for the interpretation of a sound in the context of
the immediate past. While memory traces can be observed behaviourally, the underlying
mechanisms in the auditory cortex (AC) are more elusive and can often only be observed
indirectly. One such indirect observation is repetition suppression (RS), the attenuation of
neural responses when a stimulus is presented repeatedly. This phenomenon indicates that
the auditory system contains memory traces of recent stimulation that affect responses to
incoming stimuli.
While the RS phenomenon is well established, the neuronal underpinning and factors that
modulate its lifetime are not fully understood. This thesis investigates the emergence of RS
in the AC through computational modelling and in-vivo measurements. Moreover, a robust
analysis pipeline for the determination of in-vivo RS lifetimes and an automated approach for
the optimisation of computational AC models are introduced.
Simulation results from a newly created computational model of the gerbil AC predict
that the lifetime of RS does not simply reflect recovery from short-term synaptic depres-
sion (STSD). Instead, RS is a result of the interplay between STSD dynamics and network
connectivity patterns. The same prediction also resulted from simulations with a simplified
computational model of the human AC. When network connection strengths were altered,
the lifetime of RS changed. Moreover, the gerbil AC model demonstrated that network
interactions cause variations in RS lifetime as a function of stimulus audio-frequency. Elec-
trophysiological recordings revealed audio-frequency-specific RS lifetimes in the AC of four
out of six gerbils. Moreover, the RS lifetimes deduced from the intracortical recordings were
shorter than lifetimes deduced from extracortical measurements of activity in the human AC.
In conclusion, the findings suggest that RS in the AC is a network effect. The resulting
lifetime variations across neural populations and the audio-frequency of the stimulus might
play a functional role in the context of temporal binding of sounds. The variation across
species might reflect that AC response dynamics are respectively tailored to temporal binding
across the shorter time scales of gerbil vocalisations and the longer time scales of human
speech.Ein auditives sensorisches Gedächtnis ist essentiell, um Hörreize im Kontext der unmittel-
baren Vergangenheit zu interpretieren. Während Gedächtnisspuren auf der Verhaltensebene
gut beobachtet werden können, sind die zugrunde liegenden Mechanismen im Hörkortex schwe-
rer zu fassen und meist nur indirekt zu beobachten. Eine solche indirekte Beobachtung
ist Wiederholungsunterdrückung (WU), eine Verminderung neuronaler Aktivität bei wieder-
holtem Auftreten eines Stimulus. Dieses Phänomen deutet darauf hin, dass im auditiven
System Gedächtnisspuren von vorhergehenden Stimuli existieren, die die neuronale Antwort
auf folgende Stimuli beeinflussen.
WU ist ein gut beschriebenes Phänomen, jedoch sind die neuronalen Grundlagen sowie
die Faktoren, die die Verfallszeit der Unterdrückung beeinflussen, nicht abschließend geklärt.
Diese Dissertation nutzt Computersimulationen und In-vivo-Messungen, um das Auftreten
von WU im Hörkortex zu untersuchen. Zusätzlich werden eine robuste Analyse-Pipeline für
die Ermittlung von Verfallszeiten in vivo sowie ein Ansatz für die automatisierte Optimierung
von Computermodellen des Hörkortex vorgestellt.
Die mit einem neuen Modell des Gerbil-Hörkortex erzielten Simulationsergebnisse sagen
voraus, dass Verfallszeiten der WU nicht allein die Verfallszeiten synaptischer Kurzzeitde-
pression spiegeln. Stattdessen ergibt sich WU aus der Wechselwirkung zwischen synaptischer
Kurzzeitdepression und dem Verbindungsmuster des neuronalen Netzwerkes. Dieselbe Prog-
nose resultierte auch aus Simulationen mit einem vereinfachten Computermodell des men-
schlichen Hörkortex. Änderungen der Stärke der Netzwerkverbindungen führten zu einer
Veränderung der WU-Verfallszeit. Zusätzlich war im Gerbil-Modell zu beobachten, dass auf-
grund von bestimmten Netzwerk-Interaktionen die Verfallszeit abhängig von der Audiofre-
quenz des Stimulus ist. Elektrophysiologische Messungen im Hörkortex offenbarten audio-
frequenz-spezifische Verfallszeiten bei vier von sechs Gerbilen. Außerdem waren die aus den
intrakortikalen Messungen ermittelten Verfallszeiten kürzer als die von extrakortikalen Mes-
sungen abgeleiteten Verfallszeiten für den menschlichen Hörkortex.
Die Ergebnisse deuten somit darauf hin, dass WU im Hörkortex ein Netzwerkeffekt ist.
Die sich daraus ergebenden Variationen der Verfallszeiten, über neuronale Populationen und
Stimulus-Audiofrequenzen hinweg, könnten eine Rolle bei der Verarbeitung von längeren und
komplexeren Tonsequenzen spielen. Die Variation zwischen den Spezies könnte bedeuten, dass
die Reaktionsdynamik des jeweiligen Hörkortex an die Verarbeitung der kürzeren Gerbil-Laute
beziehungsweise der längeren Sequenzen menschlicher Sprache angepasst ist.Literaturverzeichnis: Seite 125-13
The chemical space spanned by manually curated datasets of natural and synthetic compounds with activities against SARS-CoV-2
Get PDFDiseases caused by viruses are challenging to contain, as their outbreak and spread could be very sudden, compounded by rapid mutations, making the development of drugs and vaccines a continued endeavour that requires fast discovery and preparedness. Targeting viral infections with small molecules remains one of the treatment options to reduce transmission and the disease burden. A lesson learned from the recent coronavirus disease (COVID-19) is to collect ready-to-screen small molecule libraries in preparation for the next viral outbreak, and potentially find a clinical candidate before it becomes a pandemic. Public availability of diverse compound libraries, well annotated in terms of chemical structures and scaffolds, modes of action, and bioactivities are, therefore, crucial to ensure the participation of academic laboratories in these screening efforts, especially in resource-limited settings where synthesis, testing and computing capacity are scarce. Here, we demonstrate a low-resource approach to populate the chemical space of naturally occurring and synthetic small molecules that have shown in vitro and/or in vivo activities against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its target proteins. We have manually curated two datasets of small molecules (naturally occurring and synthetically derived) by reading and collecting (hand-curating) the published literature. Information from the literature reveals that a majority of the reported SARS-CoV-2 compounds act by inhibiting the main protease, while 25% of the compounds currently have no known target. Scaffold analysis and principal component analysis revealed that the most common scaffolds in the datasets are quite distinct. We then expanded the initially manually curated dataset of over 1200 compounds via an ultra-large scale 2D and 3D similarity search, obtaining an expanded collection of over 150 k purchasable compounds. The spanned chemical space significantly extends beyond that of a commercially available coronavirus library of more than 20 k small molecules and constitutes a good starting collection for virtual screening campaigns given its manageable size and proximity to hand-curated compounds
Vitamin A concentration in bovine liver and milk does not only depend on characteristics of the farming system
Get PDFThe study examined the vitamin A status in commercially managed suckler cows and lactating dairy cows and identified primary influencing factors. Liver retinyl ester concentrations were higher in multiparous than primiparous cows (p < 0.01). Pasture availability was associated with higher β-carotene concentrations (p < 0.001). In dairy cows, pasture access during the dry period did not affect any of the parameters assayed. β-Carotene and retinol in milk increased with parity. No vitamin A deficiency or hypervitaminosis A was detected. Liver and milk retinol and retinyl ester concentrations that were analysed in the present study and data from a recent German total diet study were used to estimate the exposure to preformed vitamin A in vulnerable groups (children, 0.5–5 years). 95th percentiles of preformed vitamin A intake do not exceed tolerable upper intake levels in individuals between 1 year and 5 years, but in infants 6 to 12 months of age
Die Bedeutung der objektiven Hermeneutik für das kriminalistische Denken : Fallrekonstruktion aus polizeilicher Ermittlungs- und Protokollierungspraxis
Get PDFLiteraturverzeichnis: Blatt 306-35
Exploring participants' characteristics and self-assessed readiness to conduct clinical trials in general practice : baseline analysis of the RaPHaeL practice-based research network
Get PDFBackground: Primary care is integral to healthcare systems extending beyond traditional illness management to include preventive care, chronic disease management, and health promotion. Practice-based research networks (PBRNs) have emerged as essential infrastructures for conducting clinical research in primary care. This study explores the establishment of the ‘Research-Practices Halle-Leipzig’ (RaPHaeL) PBRN in Germany, evaluating the characteristics and research readiness of participating practices. Methods: A cross-sectional survey (MORNING II) was conducted among all general practitioners (GPs) joining the RaPHaeL PBRN, assessing socio-demographic characteristics, practice infrastructure, and research readiness. After a descriptive analysis, we compared data with a previous study (MORNING) to examine potential differences between PBRN participants and non-participants. We developed a research readiness score (RRS) to quantify practices’ ability to perform clinical research subtasks. Results: The response rate was 97.1% and our participants were often male, involved in undergraduate education, generally interested in research or had previous research experiences. However, they differed widely in age and size, staff structure, and patient demographics of their practices. Initially, around two-thirds of the practices were not sufficiently prepared to conduct clinical trials (self-assessed feasibility of relevant subtasks). If further research and documentation tasks are required, patient recruitment estimations are lower than for patient identification and information. Conclusion: This study highlights the variability in research readiness among GP practices and shows the need for targeted training. By systematically assessing and enhancing research capabilities of participating GPs, PBRNs can facilitate high-quality clinical research in primary care to improve patient outcomes and healthcare delivery
Modelling decision making under risks : the case of smallholder farmers in Northern Ghana
Get PDFSmallholder farmers in semi-arid West Africa face low soil fertility, weak market access, and high weather variability, making farm investments risky and leading to poverty traps. This study applied an integrated bio-economic model to assess risk management options for smallholders in Northern Ghana. The model combines crop simulation, farm optimisation, driven by a large ensemble climate data to evaluate the impacts of index-based insurance. Results show that seed insurance with replanting incentives stabilises incomes and reduces asset losses more effectively than full-weather insurance options. However, basis risk, driven by environmental mismatches can reduce insurance effectiveness. Findings highlight the importance of context-specific risk management strategies combining risk reduction, transfer, and adaptive planning to support sustainable intensification and resilience under climate variability
Potential and constraints of organic soil amendments for long-term carbon storage and soil improvement
Get PDFThis dissertation includes four studies on organic soil amendments, with a focus on biochar. Meta-analyses showed that biochar increases soil organic carbon (SOC) more stably over time than manure. Long-term field trials confirmed biochar’s persistence in loamy soils, while losses in sandy soils were likely due to leaching. A study on biochar aging revealed changes in its properties, with co-composted biochar enhancing nitrogen retention. Overall, biochar shows high potential for long-term SOC sequestration and soil improvement, particularly when applied under appropriate site and management conditions
The role of bracken’s fronds and litter on tree seedling performance in a tropical montane forest : a trait based approach
Get PDFTropical montane forests face threats from land-use change and recurrent human-induced fires, resulting in the dominance of bracken fern (Pteridium). Bracken modifies microclimate (light, temperature, moisture), affecting seedling recruitment and soil seed bank, yet its role on succession remains unclear. Besides, dispersal limitation further delays recovery, highlighting the need for active restoration. In five studies, I found bracken fronds often facilitate establishment, recruitment and growth of large-seeded, animal-dispersed species, while litter can inhibit small-seeded recruitment. Seed addition and seedling planting under different bracken management treatments showed that removing fronds and litter impairs recruitment. A trait-based approach identified species suited to bracken conditions for restoration without the need for bracken removal. Combining both techniques with trait-focused species selection could accelerate forest recovery in fire-disturbed habitats
Sexuelle Rechte im Alten- und Pflegeheim : Können Pflegeeinrichtungen von Angeboten der Sexualassistenz profitieren? : Eine Untersuchung zur Umsetzung der sexuellen Rechte im Alten- und Pflegeheim
No full textDer Fokus der vorliegende Masterarbeit liegt auf dem Thema Sexualität im Alter. In diesem Zusammenhang soll der Frage nachgegangen werden, wie sexuelle Rechte als Menschenrechte im Kontext von Institutionen der Alten- und Pflegeeinrichtungen gewährleistet werden. Angebote der Sexualassistenz können als Möglichkeit betrachtet werden, sexuelle Rechte im Alten- und Pflegeeinrichtungen umzusetzen. In Rahmen der Untersuchung wurden sechs Interviews mit Expert*innen aus dem Feld Pflege und zwei Interviews mit Sexualassistenz geführt. Die Ergebnisse der Interviews sollen Antworten auf die Frage generieren, ob und in welcher Form Institutionen der Alten- und Pflegeeinrichtungen von Angeboten der Sexualassistenz profitieren können. Für die Analyse und Auswertung der erhobenen Daten wurde das Softwareprogramm MAXQDA verwendet. Der theoretische Hintergrund nimmt Bezug auf gesellschaftliche und politische Diskurse zu den Themenschwerpunkten Alter als Lebensphase, Sexualität sowie Sexualität im Alter, sexuelle Rechte als Menschenrechte bis ins hohe Alter und Sexualassistenz als Mittel, zur sexuellen Selbstbestimmung hilfe- und pflegebedürftiger Menschen.Literaturverzeichnis: Seite 90-10
Immunregulation der Stammzellnische in Myelodysplastischen Neoplasien : die besondere Rolle von mikroRNAs
No full textMyelodysplastische Neoplasien (MDS) sind eine Gruppe hämatopoetischer Stammzellerkrankungen, die mit einer gestörten Bildung aller Blutzellklassen einhergehen. T-Zellen, als ein Teil der Stammzellnische, leisten mit ihren Signalwegen einen wichtigen Beitrag zur Aufrechterhaltung der Hämatopoese. MikroRNAs, kurze nicht kodierende RNA Moleküle, sind wichtige Feinregulatoren fundamentaler zellbiologischer Prozesse und ihre Dysregulation ist mit den unterschiedlichsten Krebsformen assoziiert, so auch mit MDS. In der vorliegenden Arbeit wurden die in MDS differentiell exprimierten mikroRNAs miR-15a, miR-34a, miR-143, miR-150 und miR-181b in den hämatopoetischen Zelllinien MDS-L und THP-1 hinsichtlich ihres Einflusses auf verschiedenen Zellprozesse untersucht. Zusätzlich wurde ein für CD4+ und CD8+ T-Zellen spezifisches miRNA-Expressionsprofil sowohl aus MDS- als auch aus nicht-MDS-Knochenmarkproben identifiziert und einige Kandidaten hinsichtlich ihrer möglichen Funktion untersucht