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Plastification of cellulose
No full textCellulose ist die weltweit am häufigsten vorkommende Biomasseressource, und ihre günstigen Eigenschaften haben zu einer breiten Palette von Anwendungen geführt. Die komplexe Struktur der Cellulose, insbesondere ihre zahlreichen Hydroxylgruppen und die daraus resultierende Kristallinität, führt jedoch zu außergewöhnlichen mechanischen Eigenschaften und komplexen mehrstufigen Wechselwirkungen, insbesondere in Gegenwart von Wasser. Für cellulosebasierte Materialien ist ein quantitatives Verständnis dieser Strukturen und Wechselwirkungen von entscheidender Bedeutung. Ziel dieser Forschung ist es, die Bedeutung der amorph-kristallinen Struktur und der durch Wassermoleküle induzierten mechanischen Übergänge zu untersuchen, wobei der Schwerpunkt auf der Plastifizierung von cellulosebasierten Materialien liegt.
Amorphe Cellulose (AC) ist ein vollständig amorphes Cellulosepolymer mit hervorragenden mechanischen Eigenschaften und eignet sich als gutes Modellmaterial, um den strengen Zusammenhang zwischen den mechanischen Eigenschaften der Cellulose und dem molekularen Wechselwirkungszustand, insbesondere in Anwesenheit von Wasser, zu untersuchen. Für AC wurde eine Zeit-Temperatur-Feuchtigkeits-Überlagerung etabliert, die einen weiten Bereich von Temperatur und relativer Luftfeuchtigkeit (RH) abdeckt und den Frequenzbereich mechanischer Tests erheblich auf 10-11-106 Hz erweitert. Der größere feuchtigkeitsinduzierte Verschiebungsfaktor im Vergleich zum temperaturinduzierten bei der Überlagerung weist auf einen unterschiedlichen Mechanismus des AC-Relaxationsprozesses hin, der durch Wassermoleküle bzw. Temperaturänderungen hervorgerufen wird und vor allem die inter- und intramolekularen Wasserstoffbrückenbindungen (HBs) aufbricht. Die HB-Analyse auf Grundlage der FTIR-Ergebnisse belegt ebenfalls die wichtige Rolle der intermolekularen HBs für das Relaxationsverhalten von AC. Darüber hinaus wird ein Mooney-Rivlin-Modell angewendet, um den Übergang vom Dehnungs-Härten zum Dehnungs-Erweichen während des Zugversuchs zu verstehen. Dieser Übergang tritt auf und verschiebt sich zu kleineren Dehnungen, wenn entweder RH oder Temperatur erhöht wird, was ebenfalls das Überlagerungsprinzip von Feuchtigkeit und Temperatur bestätigt.
Cellulosenanokristalle (CNC) sind typische eindimensionale Nanomaterialien mit sehr hoher Kristallinität. Die einzigartige Kern-Schale-ähnliche Struktur von CNC umfasst einen kristallinen Bereich im Inneren und einen amorphen Bereich an der Außenseite. Diese Struktur hebt CNCs von anderen eindimensionalen Nanomaterialien ab und beeinflusst deren Wechselwirkungen basierend auf amorphen Celluloseketten an der Oberfläche in Anwesenheit von nanokonfiniertem Wasser. Ein Übergang von starr zu weich der Celluloseketten in amorphen Bereichen der CNC-Oberflächen wurde beobachtet, indem deren Dehnungsverhalten mit AC verglichen wurde. Dies ermöglicht die Analyse von Schwellenwerten der relativen Luftfeuchtigkeit zur Identifizierung des Hydro-Glas-Übergangsverhaltens von CNCs auf Grundlage eines Entwirrungsmodells. Es wird festgestellt, dass das nanokonfinierte Wasser, das in den amorphen Bereichen der CNCs absorbiert wird, zu einer signifikanten Wasseransammlung führt, die einen raschen Übergang der HBs von Cellulose-Cellulose- zu Cellulose-Wasser-Bindungen auslöst und nach Erreichen einer bestimmten RH zu einem plötzlichen mechanischen Verlust führt. Zudem beschleunigt das Vorhandensein von Oberflächengruppen mit niedrigeren Säuredissoziationskonstanten diesen Hydro-Glas-Übergangsprozess. Daher können selbst hochkristalline Nanomaterialien aufgrund spezifischer struktureller und interaktiver Faktoren eine Hydroplastifizierung aufweisen.
Schließlich wurde zur weiteren Realisierung der Hydroplastizität von CNC ein durch Mesoporen induzierter Dampftrainingsprozess entwickelt, um CNC-Filme unter moderatem Stress und wechselnder relativer Luftfeuchtigkeit zu formen. Unter Verwendung von aus Manteltieren gewonnenen CNCs (tCNC) mit sehr hohem Aspektverhältnis zerbrechen moderate Spannungen mit wiederholter Wasseradsorption und -desorption flaschenartige Mesoporen in kleinere Domänen. Übermäßiger Stress kann jedoch Poren teilweise schließen und gleichzeitig die Orientierung der CNCs erhöhen. Das Aspektverhältnis und die Oberflächeneigenschaften verschiedener CNCs beeinflussen ebenfalls deren Hydroplastizität. Filme mit längeren CNCs bilden größere Mesoporen, die mehr Mobilität und eine gleichmäßigere Spannungsverteilung ermöglichen, während sulfonierte oder carboxylierte CNC-Oberflächen unterschiedliche Mesoporenkonfigurationen erzeugen. Durch die Nutzung dieser Mesoporenänderungen, anstatt das Nanokristallgitter zu verändern, können stabile Formen wie helikale Filme hergestellt werden, die erstmals den Hydroplastifizierungsprozess mittels Dampftraining demonstrieren.
Diese Dissertation ist eine kumulative Arbeit, die drei Publikationen umfasst und tiefgreifende Einblicke in die Plastifizierung von Cellulose auf Grundlage von Strukturen und Wechselwirkungen bietet. Eine davon wurde bereits veröffentlicht, zwei befanden sich in Vorbereitung zur Einreichung. Der Hintergrund, die Zielsetzung der Studie, die Ergebnisse und Diskussion der drei Publikationen sowie die Schlussfolgerungen werden in den Abschnitten 1-4 dargestellt.Cellulose is the most abundant biomass resource worldwide, and its favorable properties have led to a wide range of applications. However, the complex structure of cellulose, particularly its abundant hydroxyl groups and resulting crystallinity, results in exceptional mechanical properties and intricate multi-level interactions, especially in the presence of water. For cellulose-based materials, a quantitative understanding of these structures and interactions is crucial. The goal of this research is to explore the importance of the amorphous-crystalline structure and the water molecule induced mechanical transitions, focusing primarily on the plasticization of cellulose-based materials.
Amorphous cellulose (AC) is a totally amorphous cellulose polymer with excellent mechanical properties, and can be used as a good material to investigate the rigorous relationship between cellulose mechanical properties and molecular interaction status, especially with the existence of water. A time-temperature-moisture superposition for AC covers a wide range of temperature and relative humidity (RH) was established, greatly expanding the mechanical test frequency range to 10-11-106 Hz. The larger moisture-induced shift factor compared with temperature-induced for the superposition indicate a different mechanism of AC relaxation process brought by water molecules and temperature change, which primarily break the inter- and intra-molecular hydrogen bonds (HBs), respectively. The HB analysis based on FTIR results also proves the important role of the intermolecular HB playing on the AC relaxation behaviors. Besides, a Mooney-Rivlin model is applied to understand the transition from strain hardening to softening during tensile process. This transition occurs and shifts to smaller strain when increasing either RH or temperature, which also indicate the superposition principle brought by both moisture and temperature.
Cellulose nanocrystal (CNC) is a typical one-dimensional nanomaterial with very high crystallinity. The unique core-shell like structure of CNC contains crystalline region in the interior and amorphous region on the outside. This structure sets CNCs apart from other one-dimensional nanomaterials, influencing their interactions based on amorphous cellulose chains on surface in the presence of nanoconfined water. A rigid-soft transition of cellulose chains in amorphous regions of CNC surfaces by comparing their strain behaviors with AC was observed. This allows the analysis of a threshold RH values to identify a threshold RH value to identify the hydro-glass transition behavior of CNCs based on a untangling model. It is found that the nanoconfined water absorbed within the amorphous regions of CNCs leads to significant water condensation, triggering a rapid transition of HB from cellulose-cellulose to cellulose-water type and leading to the sudden mechanical loss after reaching a certain RH. Moreover, the presence of surface groups with lower acid dissociation constants also accelerates this hydro-glass transition process. Hence, highly crystalline nanomaterials can still exhibit hydroplastification due to specific structural and interaction factors.
Finally, to further realize CNC hydroplasticity, a mesopore-induced vapor training process was developed to shape CNC films under moderate stress and alternating RH. Using tunicate-derived CNCs (tCNC) with a very high aspect ratio, moderate stress with repetitive water adsorption-desorption breaks bottle-like mesopores into smaller domains. Excessive stress, however, can partially close pores, enhancing CNC orientation at the same time. The aspect ratio and surface properties of different CNCs also affect their hydroplasticity. Films with longer CNCs form larger mesopores, allowing more mobility and uniform stress distribution, while sulfonated or carboxylated CNC surfaces produce distinct mesopore configurations. By harnessing these mesopore changes rather than altering the nanocrystal lattice, stable shapes such as helical films can be produced, demonstrating the hydroplastification process using vapor training for the first time.
This thesis is a cumulative work including 3 publications that provide deep insight into cellulose plastification based on structures and interactions. One of them had already been published, and two were being prepared for submission. The background, the objective of the study, results and discussion of the three publications and the conclusions are presented in Section 1-4.2026-07-2
Molecular mechanisms underlying silent synapse generation and their role in drug-associated behaviors
No full textSilent synapses are immature glutamatergic connections that express stable NMDARs, while AMPARs are absent. These synapses are abundant during early development and serve as plasticity substrates, offering synaptic opportunities to reorganize neural networks. In the adult brain, repetitive exposure to cocaine generates de novo silent synapses in the nucleus accumbens (NAc). Although network adaptations in the NAc might contribute to regulating drug-associated behaviors involving motivation and action, they do not fully account for all aspects of addiction. Here, using the electrophysiology procedure of minimal stimulation with synaptic failure analysis, I found that cocaine also increases silent synapses in the dorsal striatum and hippocampus, but not in other areas tested. The emergence of silent synapses in those areas suggests their involvement in processes such as habitual or compulsive drug use and associative learning.
Astrocyte-neuronal crosstalk via thrombospondins (TSPs) and their neuronal receptor α2δ-1 is required for cocaine-induced silent synapse generation in the NAc. Using AAV-mediated knockdown, I found that α2δ-paralogs were differentially required throughout the brain for developmental and cocaine-induced silent synapse generation. Specifically, α2δ-1 was necessary in the striatum and α2δ-3 in the visual cortex, but both α2δ-1 and α2δ-3 were necessary in the hippocampus. This mechanistic diversity suggests why disrupting α2δ-1 function alone had previously limited effects on drug-associated behaviors. Together, these findings support the existence of distinct synapse subtypes defined by their molecular composition, which may underlie functional heterogeneity across neural networks.
However, the α2δ-family lacks intracellular domains to transduce TSP-triggered signaling. To obtain a blueprint of the neuronal and astrocytic machinery involved in cocaine-induced silent synapse generation, I tested for proteins known to be involved in synaptogenesis and able to bind to TSPs, using knockdown strategies. The numerous identified proteins are involved in membrane morphology and cell adhesion regulation and likely participate in specific stages of the synaptogenic process. I propose that (1) α2δ-paralogs and integrins act as molecular bridges between pre- and postsynaptic compartments through TSP binding, (2) BAI, Fzd9, and Celsr neuronal receptors may transduce synaptogenic signals, such as TSP-signaling, and (3) Vangl proteins may serve as auxiliary subunits to modulate and fine-tune the process. Ultimately, these components likely converge on a shared intracellular signaling cascade. This thesis identified PSD-95β as a key mediator of the synaptogenic signaling cascade in the striatum with its N-terminal domains, specifically the L27 domain and interactions with the PDZ domains, mediating the signaling.
Focusing on the astrocytic contribution, I utilized astrocyte-specific DREADD-hM3Dq activation and found that stimulating these cells alone was sufficient to generate silent synapses. Our follow-up findings suggest that this effect is dependent on mGluR5 and/or σ1, the latter being known to bind to cocaine.
At a behavioral level, inhibition of σ1 prevented cocaine-induced locomotor sensitization, which is dependent on silent synapse generation and is a proxy for increased incentive salience with repeated drug exposure. These results support my hypothesis that astrocytic σ1 functions as a cocaine receptor, mediating its behavioral effects by generating silent synapses in neighboring neurons. To link CP-AMPARs, known to mediate cue-induced drug-craving and set the threshold for cocaine-memory retrieval, to silent synapse generation, I blocked α2δ-1 with gabapentin. As a result, CP-AMPAR expression was prevented, but not drug-associated memories. These findings crystallize a therapeutic potential to prevent drug craving by targeting silent synapse generation to prevent CP-AMPAR expression.
Moreover, I used PSD-95 KO mice as a model of impaired silent synapse maturation. These mice showed impaired long-term memory retrieval but not retention, as previously thought. Notably, cue-induced rescue of this impairment correlated with the incorporation of CP-AMPARs, suggesting that these receptors might represent an active memory trace. Thus, CP-AMPARs may provide a novel approach to monitor and manipulate drug-associated memories or active memory traces in a generalized manner. Furthermore, non-contingent cocaine exposure erased drug-associated memories in PSD-95 KO and PSD-95 heterozygous mice but not in WT mice, indicating that the lack of synaptic strengthening through synaptic maturation facilitates the disruption of drug-associated memories. This finding is of great clinical relevance for the amelioration of drug-associated behaviors as associative memories typically trigger relapse and compulsive drug consumption.
In summary, this thesis elucidated the molecular machinery underlying silent synapse generation, providing a blueprint of the involved signaling components and identifying novel molecular targets to manipulate the process. By leveraging this molecular knowledge, I reveal that silent synapse-based drug-associated behaviors, such as locomotor sensitization, can be prevented. Additionally, I analyzed the role of silent synapse maturation in drug-associated memories. This maturation proved essential for long-term memory retrieval and stability, providing novel insights into how stable memories are formed and can be erased. These findings propose a target with important clinical implications for drug addiction.2026-06-2
Interfacial Protons vs. Bulk Protons: How Proton Localization Alters ATP Synthase Activity
No full textDiese Dissertation untersucht Protonentransferprozesse an biologischen Membranen mit besonderem Fokus auf die Rolle der FOF1 ATP-Synthase als Protonenkonsument. Die ATP-Synthase spielt eine zentrale Rolle in der zellulären Energieumwandlung, indem sie einen Protonengradienten zur Synthese von ATP nutzt. Allerdings bleibt die genaue Herkunft dieser Protonen – ob aus dem wässrigen Medium oder durch lateralen Transport entlang der Membranoberfläche – unklar. Ziel dieser Arbeit war es, herauszufinden, ob die ATP-Synthase bevorzugt Protonen aus bestimmten Quellen nutzt und wie diese Protonen das Protein erreichen. Zu diesem Zweck wurden verschiedene Modellsysteme auf Basis von großen unilamellaren Vesikeln (LUVs) entwickelt, die die TFOF1 ATP-Synthase aus dem thermophilen Bacillus PS3 enthielten. Als Protonenquellen wurden die wasserlösliche Fotosäure HPTS, welche Protonen im wässrigen Medium freisetzt, sowie das amphiphile Derivat C12-HPTS, welches Membran-adhärierte Protonen freisetzt, verwendet. Durch den Vergleich dieser Systeme wurde der Einfluss der Protonenlokalisierung auf die Aktivität der ATP-Synthase untersucht. Die Vesikelmodelle wurden hinsichtlich ihrer Größe, der Effizienz der Proteinintegration und der Orientierung der Proteine charakterisiert. Die erfolgreiche Rekonstitution der ATP-Synthase wurde bestätigt. Die Fotoazidität von HPTS und C12-HPTS wurde mittels Absorptions- und Fluoreszenzspektroskopie analysiert und zeigte, dass beide Verbindungen nach Lichtanregung effektiv Protonen freisetzen. Die enzymatische Aktivität wurde mit einem lumineszenz-basierten ATP-Synthese-Assay untersucht, während zeitkorrelierte Einzelphotonenzählung (TCSPC) zeitaufgelöste Einblicke in die Protonentransferdynamik lieferte. Die Ergebnisse zeigten, dass ATP-Synthase bevorzugt membran-adhärierte Protonen zur ATPProduktion nutzt, was durch erhöhte Protonentransferraten und Hinweise auf eine gesteigerte ATP-Synthese in Systemen mit C12-HPTS gestützt wurde. Diese Erkenntnisse unterstreichen die Bedeutung membrangebundener Protonenquellen für die ATP-Synthese und liefern wertvolle Einblicke in Protonentransfermechanismen an biologischen Membranen. Diese Arbeit trägt zum grundlegenden Verständnis bioenergetischer Prozesse bei und könnte potenzielle Anwendungen in der Biotechnologie ermöglichen, insbesondere zur Optimierung des Protonentransports für die Energiegewinnung.This dissertation investigates proton transfer processes at biological membranes, focusing on the role of FOF1 ATP synthase as a proton consumer. ATP synthase plays a central role in cellular energy conversion by utilizing a proton gradient to synthesize ATP, yet the exact origin of these protons – whether from the bulk medium or transported along the membrane
surface – remains unclear. The aim of this study was to determine whether ATP synthase preferentially utilizes protons from specific sources and to understand the mechanisms behind proton transfer to the protein. To address these questions, various model systems were developed using large unilamellar vesicles (LUVs) containing the TFOF1 ATP synthase from thermophilic Bacillus PS3. Proton sources included the water-soluble photoacid HPTS, mimicking bulk protons, and the amphiphilic derivative C12-HPTS, which releases protons attached to the membrane. By comparing these systems, the influence of proton localization on ATP synthase activity was evaluated. The vesicular models were characterized in terms of size, protein reconstitution efficiency, and protein orientation, with successful protein insertion confirmed. The photoacidity of both HPTS and C12-HPTS was assessed using absorbance and fluorescence spectroscopy, revealing that both compounds effectively release protons upon light excitation. A luminescence-based ATP synthesis assay was used to evaluate enzymatic activity, and time-correlated single photon counting (TCSPC) provided time-resolved insights into proton transfer dynamics.
The results indicated that ATP synthase preferentially utilizes membrane-bound protons over bulk protons for ATP production, as evidenced by higher proton transfer rates and hints on an increased ATP production in systems containing C12-HPTS. These findings underscore the significance of membrane-bound proton sources for ATP synthesis and provide valuable insights into proton transfer mechanisms at biological membranes. This work contributes to the fundamental understanding of bioenergetic processes and has potential implications for biotechnological applications aimed at optimizing proton transport for energy production.2026-04-1
Comparative Analysis of Interstitial Lung Diseases in Autoimmune Disorders
No full textDas Antisynthetase-Syndrom und die systemische Sklerodermie werden zu den Kollagenosen gezählt. Die pulmonale Beteiligung dieser Krankheiten, in Form einer interstitiellen Lungenerkrankung, erhöht die Mortalität und Morbidität betroffener Patienten deutlich. Ein schnelles medikamentöses Eingreifen ist deswegen unerlässlich. Beide Erkrankungen zählen zu den seltenen Erkrankungen. So gibt es nur eine begrenzte publizierte Datenmenge über den Verlauf der Kollagenosen-assoziierten interstitiellen Lungenerkrankung. Das Ziel dieser Studie ist es, den radiologischen Verlauf der interstitiellen Lungenerkrankung während der immunsuppressiven Behandlung zu untersuchen. Betrachtet wurden alle Patienten der Klinik für Nephrologie und Rheumatologie der Universitätsmedizin Göttingen, die typische klinische Merkmale und/oder Laborbefunde des Antisynthetase-Syndroms oder der systemischen Sklerodermie aufwiesen. Inkludiert wurden jene Patienten, bei denen eine interstitielle Lungenerkrankung in der Bildgebung vorhanden war; ausgeschlossen wurden Patienten ohne Lungenbeteiligung und Patienten mit unvollständigen Datensätzen. Ein intensives Krankenaktenstudium wurde durchgeführt, um retrospektiv demographische und klinische Daten, Laborparameter, Lungenfunktionstestparameter, radiologische Bildgebungen und medikamentöse Behandlungsschemata zu sammeln und zu analysieren. Das Ausmaß von Milchglasinfiltraten, fibrotischen Veränderungen und Honigwabenbildung wurde anhand von hochauflösenden Thorax-Computertomographien analysiert und bewertet. Zwei Radiologen bewerteten unabhängig voneinander das Ausmaß der interstitiellen Lungenerkrankung in den Thorax-Computertomographie-Aufnahmen bei Diagnose und im Verlauf der Erkrankung. Zusätzlich wurde eine Stratifizierung der Patienten vorgenommen. Bei Antisynthetase-Syndrom-Patienten erfolgte diese nach einer erhaltenen Therapie mit Rituximab oder eine medikamentöse Behandlung ohne Anwendung von Rituximab (Rituximab ever vs. Rituximab never). Probanden mit systemischer Sklerodermie wurden anhand ihrer Erkrankungsform in eine Gruppe mit limitierter systemischer Sklerodermie und mit diffuser systemischer Sklerodermie eingeteilt.
Insgesamt wurden zwölf Patienten mit Antisynthetase-Syndrom-assoziierter interstitieller Lungenerkrankung und 28 Patienten mit systemischer Sklerodermie-assoziierter interstitieller Lungenerkrankung in diese Studie eingeschlossen. Bei Patienten mit Antisynthetase-Syndrom erbrachten Lungenfunktionstestungen einen stabilen Verlauf der Parameter. Die der interstitiellen Lungenerkrankung zugehörigen Veränderungen verbesserten in den Thorax-Computertomographie-Nachuntersuchungen bei der Mehrzahl der Patienten unter immunsuppressiver Therapie. Einen signifikanten Unterschied zwischen der Rituximab ever- und der Rituximab never-Gruppe konnten wir nicht feststellen, wohl aber, dass Rituximab eher bei schwerer erkrankten Patienten mit Myositis und einer schubartigen Erkrankungsform Einsatz fand.
Systemische Sklerodermie-Patienten präsentierten, im Vergleich zu den Antisynthetase-Syndrom-Patienten, meist ein anfänglich weniger akutes Krankheitsbild. Die Veränderungen der interstitiellen Lungenerkrankung nahmen, wenn auch nicht signifikant, im Verlauf zu und zeigten so eine gegensätzliche Entwicklung verglichen zu Patienten mit Antisynthetase-Syndrom. Initial waren die Gesamt-Scores der Gruppe mit der diffusen Form der systemischen Sklerodermie signifikant erhöht, glichen sich jedoch zur letzten vorhandenen Computertomographie den Scores der Gruppe mit limitiert kutaner systemischer Sklerodermie an.
Da Rituximab bei Antisynthetase-Syndrom-Patienten mit schwerer oder schubartiger Erkrankung genutzt wurde, ist es positiv zu bemerken, dass die Endergebnisse in dieser Gruppe (Rituximab ever) ähnlich denen in der zumeist weniger schwer erkrankten Kohorte (Rituximab never) waren. Für diese stärker betroffenen Patienten kann Rituximab anderen Medikationen überlegen sein. Um Antisynthetase-Syndrom-Patienten schnell einer richtigen und erkennbar wirkungsvollen Therapie zuzuführen, unterstützen wir außerdem Forderungen nach einheitlichen Klassifikationskriterien. Bei Patienten mit systemischer Sklerodermie-assoziierter interstitieller Lungenerkrankung zeigten die Computertomographie-Scores eine steigende Tendenz, während sich bei den Lungenfunktionstestungen ein insgesamt stabiler Verlauf ohne klinisch relevante Verschlechterung abzeichnete. Auch wenn das erfreulich ist, verdeutlichen unsere Ergebnisse die Wichtigkeit von regelmäßigen Nachuntersuchungen. So kann auf eine Progression der interstitiellen Lungenerkrankung oder auf weitere Manifestationen der systemischen Sklerodermie, wie eine pulmonale Hypertonie, reagiert werden. Neu ist dabei die Erkenntnis, dass Patienten mit einer limitierten Form ähnlich schwere Verläufe der interstitiellen Lungenerkrankung erleiden können. Bei initial signifikant niedrigeren Scores im Vergleich zu Patienten mit der diffusen Form, hatten sich die Gesamt-Scores dieser Kohorte zum letzten untersuchten Zeitpunkt (nach im Median 5 Jahren) denen der Probanden mit diffus kutaner systemischer Sklerodermie angeglichen. Diese Patienten sind also gerade im Verlauf der Erkrankung nicht minder gefährdet und müssen regelmäßig nachuntersucht und eventuell medikamentös umgestellt werden. Die gleichbleibenden Scores der Patienten mit diffus kutaner systemischer Sklerodermie im Verlauf können ein Hinweis auf die gute Ansprache unter ausgeprägter Therapie sein. Trotz insgesamt zufriedenstellenden Ergebnissen bei Patienten mit systemischer Sklerodermie-assoziierter interstitieller Lungenerkrankung sollte auch der Einsatz neu bekanntgewordener Therapieoptionen wie z. B. Nintedanib erwogen werden. In Zukunft sollten prospektive Studien mit vorab festgelegten Endpunkten durchgeführt werden, um die Auswirkung medikamentöser Therapie auf den Verlauf und das Outcome von Kollagenose assoziierter interstitiellen Lungenerkrankung weiter zu untersuchen und das Wissen darüber zu stärken und mehren. Gerade wenn sich, wie jüngst bei der systemischen Sklerodermie, neue Therapiemöglichkeiten und Perspektiven bieten, muss konsequent an retro- wie auch prospektiver Datenerfassung zu diesem Thema gearbeitet werden. Die Ergebnisse unserer Studie können als Grundlage dafür hilfreich sein. So und durch interdisziplinäre Zusammenarbeit kann langfristig eine optimale Betreuung, inklusive der Senkung von Mortalität und Morbidität sowie Steigerung der Lebensqualität, gewährleistet werden. Dies sollte, gerade bei Patienten mit seltenen Erkrankungen, wie jenen aus dem Formenkreis der Kollagenosen, mit höchster Priorität fokussiert werden.The Antisynthetase syndrome and Systemic Sclerosis are classified as connective tissue diseases. Pulmonary involvement in these diseases, in the form of interstitial lung disease (ILD), significantly increases the mortality and morbidity of affected patients. Rapid medical intervention is therefore essential. Both conditions are rare diseases, resulting in a limited amount of published data on the course of connective tissue-associated interstitial lung disease. The aim of this study is to investigate the radiological course of interstitial lung disease during immunosuppressive treatment.
We examined all patients at the Department of Nephrology and Rheumatology at the University Medical Center Göttingen who showed typical clinical features and/or laboratory findings of Antisynthetase syndrome or systemic sclerosis. Patients with ILD present on imaging were included; patients without lung involvement and those with incomplete datasets were excluded.
An intensive review of patient files was performed to retrospectively collect and analyze demographic and clinical data, laboratory parameters, lung function test parameters, radiological imaging, and drug treatment regimens. The extent of ground-glass opacities, fibrotic changes, and honeycombing was analyzed and assessed using high-resolution chest computed tomography. Two radiologists independently evaluated the extent of ILD in the chest CT scans at diagnosis and during the course of the disease. In addition, patients were stratified. For Antisynthetase syndrome patients, stratification was based on whether they received Rituximab treatment (Rituximab ever vs. Rituximab never). Subjects with Systemic Sclerosis were divided into groups based on their disease form: limited systemic sclerosis and diffuse systemic sclerosis.
A total of twelve patients with Antisynthetase syndrome-associated ILD and 28 patients with Systemic Sclerosis-associated ILD were included in this study. In patients with Antisynthetase syndrome, lung function tests showed a stable course of parameters. The ILD-related changes improved in the follow-up CT scans in the majority of patients under immunosuppressive therapy. We could not find a significant difference between the Rituximab ever and Rituximab never groups, but we did observe that Rituximab was more often used in more severely ill patients with myositis and a relapsing-remitting disease course.
Compared to Antisynthetase syndrome patients, Systemic Sclerosis patients usually presented with a less acute initial clinical picture. The ILD changes, although not significantly, increased over time, showing a contrasting development compared to patients with Antisynthetase syndrome. Initially, the total scores of the group with the diffuse form of systemic sclerosis were significantly elevated, but they approximated the scores of the group with limited cutaneous systemic sclerosis by the last available CT scan.
Since Rituximab was used in Antisynthetase syndrome patients with severe or relapsing disease, it is a positive observation that the final results in this group were similar to those in the generally less severely ill cohort. For these more affected patients, Rituximab may be superior to other medications. To quickly provide Antisynthetase syndrome patients with a correct and recognizably effective therapy, we also support calls for uniform classification criteria.
In patients with Systemic Sclerosis-associated ILD, the CT scores showed an increasing tendency, while lung function tests indicated an overall stable course without clinically relevant deterioration. While this is encouraging, our results highlight the importance of regular follow-up examinations. This allows for a reaction to the progression of ILD or to other manifestations of Systemic Sclerosis, such as pulmonary hypertension. A new finding is the realization that patients with a limited form can suffer similarly severe ILD courses. Despite initial significantly lower scores compared to patients with the diffuse form, the total scores of this cohort had aligned with those of subjects with diffuse cutaneous Systemic Sclerosis by the last examined time point (after a median of 5 years). These patients are therefore not less at risk, especially in the course of the disease, and must be regularly monitored and potentially undergo changes in medication. The consistent scores of patients with diffuse cutaneous Systemic Sclerosis over time may be an indication of a good response under intensive therapy. Despite overall satisfactory results in patients with Systemic Sclerosis-associated ILD, the use of newly emerged therapeutic options such as Nintedanib should also be considered.
In the future, prospective studies with predetermined endpoints should be conducted to further investigate the impact of drug therapy on the course and outcome of connective tissue disease-associated ILD and to strengthen and increase knowledge about it. Especially when new therapeutic possibilities and perspectives arise, as recently seen in Systemic Sclerosis, consistent work on both retrospective and prospective data collection on this topic is necessary. The results of our study can serve as a foundation for this. In this way, and through interdisciplinary collaboration, optimal care, including the reduction of mortality and morbidity and the enhancement of quality of life, can be ensured in the long term. This should be focused on with the highest priority, especially for patients with rare diseases, such as those within the spectrum of connective tissue diseases.2026-02-1
Ergebnisse mikroskopischer und röntgenologischer Untersuchungen zur Differentialdiagnose von Krankheitsspuren an ausgewählten Skeletproben der frühbyzantinischen Kinderpopulation vom Arslantepe/Malatya (Türkei)
No full textThis study shows that the microscopic analysis of bone samples can provide reliable diagnoses of disease burdens. In this case, the analysis was used to study an early Byzantine child population in southern Central Anatolia.
In anthropology and archaeology, skeletal remains are typically examined macroscopically and, in select cases, by radiography. However, this method does not always lead to reliable diagnoses, as diagenetic factors affecting the bones over time can simulate macroscopic signs of disease. These signs can usually be clarified through microscopic analysis.
This paper highlights the possibilities and limitations of paleopathological examination. The evaluation focuses on detecting deficiency diseases, such as scurvy, rickets, and anemia.
The examined skeletal remains originate from the well-known Arslantepe site, an excavation site near Malatya in present-day Turkey. Early Byzantine children's skeletons from this period (600-800 CE) were examined macroscopically, microscopically, and radiologically, and the results were compared.
Traces of disease on the skeletal remains allow us to draw conclusions about the social, political, and cultural conditions of populations at that time.2026-03-0
Validation of a German version of the Central Sensitization Inventory (CSI-GE)
No full textDas Phänomen der Zentralen Sensibilisierung wird als ein Faktor für die Entstehung und Unterhaltung verschiedener chronischer Schmerzsyndrome angesehen. Die Quantifizierung dieses Prozesses in Klinik und Forschung ist ein schwieriges Unterfangen. Das Central Sensitization Inventory (CSI) wurde entwickelt, um die Detektion von Zentraler Sensibilisierung und central sensitivity syndroms (CSS) in einfacher Form mittels eines Fragebogens zu ermöglichen. Ziel dieser Arbeit war die Validierung einer in die deutsche Sprache übersetzten und kulturell adaptierten Version des CSI (im Folgenden CSI-GE) sowie kritische Diskussion der Ergebnisse im Kontext internationaler Studien. Die Analyse des CSI-GE untersuchte einerseits die Reliabilität, andererseits die Validität des Instruments. Bezüglich der Reliabilität wurde die Interene Konsistenz mittels Cronbachs α und die Test-Retest Reliabilität in einer Subgruppe chronischer Schmerzpatient*innen mittels Intraklassenkorrelationskoeffizienten (ICC) analysiert. Die Analyse der Validität gliedert sich in die strukturelle Validität und die Konstruktvalidität. Die Untersuchung der strukturellen Validität erfolgte in Form einer explorativen und konfirmatorischen Faktorenanalyse. Für die Konstruktvalidität wurde im Rahmen von Hypothesentestungen einerseits das Differenzierungsvermögen des CSI-GE zwischen Subgruppen untersucht, von welchen vorab angenommen wurde, dass ein unterschiedliches Ausmaß Zentraler Sensibilisierung vorliegt. Andererseits wurden konvergente beziehungsweise divergente Eigenschaften zu bekannten, bereits etablierten Fragebögen und Konstrukten mittels Korrelationen analysiert. Insgesamt wurden 346 Proband*innen rekrutiert, was in 310 auswertbaren Datensätzen resultierte. Diese teilen sich auf in 247 chronische Schmerzpatient*innen, bestehend aus fünf Subgruppen, und einer schmerzfreien Kontrollgruppe mit 63 Proband*innen. Der CSI-GE zeigte eine exzellente Reliabilität mit einem Cronbachs α von 0,928 sowie einem ICC von 0,917 für die Messwiederholung nach durchschnittlich 18,42 Tagen. Die Analyse der strukturellen Validität resultierte explorativ in einer Ein-Faktor-, sowie konfirmatorisch in einer Bi-Faktor-Lösung und untermauerte die Legitimität, einen Summenwert aus allen 25 Items des Fragebogens zu bilden. Die Bedeutung weiter differenzierender Faktoren bleibt aktuell dabei noch unklar. Die Konstruktvalidität zeigte divergierende Ergebnisse. Der CSI- GE konnte signifikant zwischen Personengruppen differenzieren, von welchen im Voraus angenommen wurde, dass sie ein unterschiedliches Ausmaß Zentraler Sensibilisierung aufweisen. Zusätzlich erzielte die Subgruppe mit Fibromyalgie als „Positivkontrolle“ für das Ausmaß Zentraler Sensibilisierung die höchsten und die schmerzfreie Kontrollgruppe als „Negativkontrolle“ die niedrigsten Werte. Die Beziehung zu anderen Konstrukten zeigte den höchsten Zusammenhang mit somatischen Symptomen. Schmerzsensitivität, Intensität, Dauer und physische gesundheitsbezogene Lebensqualität scheinen keine bedeutende Rolle im Konstrukt einzunehmen. Die Interpretation der Ergebnisse ist schwierig, da die Definitionen Zentraler Sensibilisierung stark unterschiedlich sind, assoziierte Symptome sehr unspezifisch erscheinen und somit die Items im Fragebogen wenig spezifisch ausfallen. Es bleibt im Hinblick auf diese Aspekte zweifelhaft, ob der CSI-GE Zentrale Sensibilisierung oder eher ein Ausmaß polysymptomatischer Beeinträchtigung misst. Diese polysymptomatische Beeinträchtigung könnte in gleicher Weise das Differenzierungsvermögen zwischen den Subgruppen erklären, aber auch den prominenten Faktor aus der Faktorenanalyse repräsentieren. Zusätzlich lässt sich die Beziehung einiger bereits etablierter Instrumente zum CSI-GE nur schwierig erklären und passt nicht in das aktuelle Verständnis von Zentraler Sensibilisierung. Dies betrifft insbesondere die niedrige Korrelation mit dem „Pain Sensitivity Questionnaire minor“ in der hier durchgeführten Studie, jedoch auch die nicht vorhandenen oder geringen Zusammenhänge experimentell ermittelter Druckschmerzschwellen und dem CSI in anderen internationalen Studien. Ein essenzieller Aspekt von Zentraler Sensibilisierung – eine reduzierte Schmerzschwelle – korreliert nicht mit dem klinischen Syndrom. Dies untermauert, dass der CSI eher psychopathologische Aspekte Zentraler Sensibilisierung beziehungsweise von CSS erfasst, als neurobiologische Alterationen. Ein alltäglicher klinischer und wissenschaftlicher Nutzen des Instruments, z.B. zur Therapieplanung und Verlaufskontrolle erscheint zum aktuellen Zeitpunkt voreilig. In weiteren Studien sollte zunächst das Konstrukt weiter konkretisiert, sowie die Änderungssensitivität des Fragebogens nach Interventionen analysiert werden.Central sensitization is considered an important factor in the development and maintenance of various chronic pain syndromes. Quantifying this process is challenging. The Central Sensitization Inventory (CSI) was developed to facilitate the detection of central sensitization and central sensitivity syndromes (CSS) using a simple questionnaire. The aim of this study was to validate a German, culturally adapted version of the CSI (CSI-GE) and to critically discuss the results in the context of international studies.
The analysis of the CSI-GE examined both the reliability and validity of the instrument. The validity analysis was divided into structural validity and construct validity. Structural validity was investigated using factor analysis. For construct validity, hypothesis testing was conducted to examine the CSI-GE's ability to differentiate between subgroups presumed to have varying degrees of central sensitization. Additionally, correlations with well-established questionnaires and related constructs were analyzed.
A total of 346 participants were recruited, resulting in 310 usable data sets. These 310 data sets consisted of 247 chronic pain patients and 63 pain-free participants. The CSI-GE demonstrated excellent reliability, with Cronbach's α of 0.928. Test–retest reliability yielded an ICC of 0.917 for the repeated measures after an average interval of 18.42 days. The structural validity analysis yielded a one-factor solution in the exploratory analysis and indicated the best fit for a bifactor solution in the confirmatory analysis, thus supporting the legitimacy of calculating a sum score across all 25 questionnaire items. The significance of further differentiating factors remains unclear.
Construct validity showed mixed results. The CSI-GE was able to significantly differentiate between groups of individuals presumed to have varying degrees of central sensitization. The fibromyalgia subgroup, as a “positive control,” had the highest scores, and the pain-free group, as a “negative control,” had the lowest. The relationships with other constructs showed the strongest correlations with somatic symptoms. Pain sensitivity, pain intensity, pain duration, and physical health-related quality of life do not appear to play a significant role in the construct.
Interpreting the results was challenging because definitions of central sensitization vary considerably, associated symptoms appear nonspecific, and the questionnaire items consequently lack specificity. Given these aspects, it remains questionable whether the CSI-GE measures central sensitization or rather the extent of polysymptomatic impairment. This polysymptomatic impairment could equally explain the instrument’s ability to differentiate between subgroups and may also represent the dominant factor identified in the factor analysis. Furthermore, the relationships between some established instruments and the CSI-GE are difficult to explain and do not align with the current understanding of central sensitization. This is particularly evident in the low correlation with the Pain Sensitivity Questionnaire Minor observed in the present study, as well as in the absence or weakness of correlations between experimentally determined pressure pain thresholds and the CSI reported in other international studies. A key aspect of central sensitization, a reduced pain threshold, is not reflected in the clinical syndrome measured by the CSI. This finding supports the notion that the CSI primarily captures psychopathological aspects of central sensitization or CSS rather than fundamental neurobiological changes.
At present, routine use of the instrument in clinical practice or research, for example for treatment planning and monitoring, appears premature. Further studies should first refine the underlying construct and analyze the questionnaire’s sensitivity to change following therapeutic interventions.2026-02-1
Computational Studies on Ruthenium-Catalyzed Site-Selective C–H Activation
No full textOver the past decades, the direct modification of C–H bonds without prefunctionalization has emerged as a powerful strategy for constructing C–C and C–Het bonds, with broad applications in crop protection, pharmaceutical chemistry, and material sciences. Ruthenium catalysis and photo-ruthenium-catalysis have proven particularly effective for the selective functionalization of specific inert C–H bonds. Beyond developing mild reaction conditions to achieve these transformations, a deep understanding of the underlying reaction mechanism is crucial for further advancements. Such insights enable chemists to modify reactions, thereby improving yield and selectivity. Additionally, computational chemistry plays a vital role in interpreting and rationalizing experimental data, facilitating the design of new ligands and molecules with tunable properties. This thesis explores novel synthetic strategies for ruthenium-catalyzed site-selective C–H functionalizations, with a particular emphasis on the mechanistic studies to elucidate the reactivity and selectivity.2026-12-0
Neurocognitive Mechanisms of Social Information Use in Perception and Decision-making
No full textSocial information is pervasive and guides human perception and decision-making, particularly
under conditions of uncertainty. Social information use is jointly governed by its external
characteristics—such as emotional content, informational content, evaluative tone, and proximity
to one’s prior judgments and decisions—and internal metacognitive monitoring processes that
assess confidence in one’s perceptions and decisions. However, the underlying neurocognitive
mechanisms of this joint influence remain insufficiently understood. This dissertation integrates
findings from two EEG studies to propose a unified neurocognitive framework for how social
information shapes perception and decision-making. Study 1 employed a two-day experimental
design. On Day 1, an associative learning paradigm paired facial expressions (social condition)
with briefly presented, perceptually uncertain target stimuli (images of environmental objects and
scenes), compared to a no-social control. On Day 2, memory for the learned associations was tested.
Study 2 used a Judge–Advisor task in which participants made numerical estimates and then
received either feedback (“good”/ “bad”) or advice (an alternative estimate), experimentally
manipulated in proximity to their initial estimate. In both studies, event-related potentials (ERPs)
were used to trace the temporal dynamics of social information use. Metacognitive monitoring was
assessed implicitly through classification accuracy of target stimuli (Study 1) and explicitly through
confidence ratings (Study 2). Across both domains, early stages of processing revealed an influence
of metacognitive monitoring depending on the characteristics of social information. In perception,
the P1 amplitudes indexed early sensory attention to target stimuli, which increased when target
stimuli valence was uncertain and social information conveyed emotional content. In contrast, the
P1 amplitudes decreased when internal evaluations were strong and social information aligned with
it. In decision-making, FRN amplitudes reflected confidence-dependent performance
monitoring—attenuating for feedback as confidence increased but persisting for advice, consistent
with its higher informational content. At intermediate stages, motivational salience was amplified
when social information validated confidently held perceptions and decisions. EPN increased for
accurately classified positive target stimuli paired with congruent social information, while P300
amplitudes increased for high- compared to low-proximity, with this difference being more
pronounced as confidence increased, across both feedback and advice. At later stages, LPC effects
indexed task relevance and evaluative closure. In perception, associated social information in the
learning session, attenuated LPC for negative target stimuli in the test session, suggesting reliance
on external evaluation rather than elaborative reprocessing of aversive content, whereas in
decision-making, feedback elicited stronger LPCs than advice, whereas advice produced
confidence- and proximity-dependent delays in LPC onsets, consistent with greater elaboration
between confidence and social information. Together, these findings outline a hierarchical
neurocognitive processing: characteristics of social information evaluated by metacognitive
monitoring guide social information use for uncertainty reduction at early stages; motivational
salience of social information and confident internal states gives rise to a social validation effect
reflected at the intermediate stages; and task relevance governs goal-directed use of social
information at later stages.2026-02-2
Axial and Equatorial Ligand Effects of Bioinspired Tetracarbene Iron Models for Heme and Non-Heme Enzymes
No full textThe selective oxidation of hydrocarbons with sustainable oxidants is still a challenging reaction in industry. In order to create a sustainable future—especially in regard of progressing climate change—finding alternative oxidation processes is of high interest. In this regard, inspiration from nature can help. For example, natural enzymes can perform the hydroxylation of earth-abundant hydrocarbons at ambient conditions and with high rates. Inspired by enzymes containing iron in the active center, chemists have developed model complexes to understand how the intermediates of such enzymes can perform those challenging reactions. In this work, model complexes in multiple oxidation states with different equatorial tetracarbene macrocycles as well as various axial ligations were synthesized and fully characterized, analyzing their electronic structure and reactivity.
Building on previous results on organometallic tetracarbene iron(II) complexes 1, missing spectroscopical data were added in this work and a detailed study of the equatorial ligand perturbation was carried out. In this regard, the influence of peripheral substitution of H-atoms by methyl groups as well as the modification of the ring size (18-membered vs. 16-membered macrocycles) was investigated. In addition, series of low-spin tetracarbene iron(III) complexes 2 and intermediate-spin tetracarbene iron(III) complexes 3 were synthesized and spectroscopically analyzed, in which the spin-state change could be induced by variation of solvent.
Due to the relevance of thiolato complexes in nature, for example the coordination of the cysteinato ligand to multiple high-valent active centers in enzymes, the effect of thiolato coordination on the iron(II) platform was studied in greater detail. Therefore, the 18-membered complexes 1 were reacted with different thiolate salts to obtain iron(II) complexes with different trans-axial thiolato ligands, as well as different equatorial ligations. Hereby, a series of thiolatoiron(II) complexes 4 and 5 was obtained, showing variations in spin-state and coordination geometry, emphasizing the flexibility of the tetracarbene platform. The electronic structure and geometry of those complexes was studied in detail in solid-state as well as in solution by (field-dependent) Mössbauer spectroscopy, SQUID measurements, NMR, IR and UV-Vis spectroscopic studies as well as with cyclic voltammetry.
In addition, two series of oxidoiron(IV) complexes based on the 18-membered equatorial macrocycles with different axial ligands (MeCN coordination (6), trifluoroacetato (7) and thiolato ligation (8 and 9)) were investigated. Previous spectroscopic studies on 6-18H, 7-18H and 8-18H were expanded in this work and complexes 9-18H, 6-18Me, 7-18Me and 8-18Me were newly synthesized. The substituted tetracarbene oxidoiron(IV) complexes were further characterized using UV/Vis, (field-dependent) Mössbauer, IRPD spectroscopy, SQUID magnetometry and crystallography (in the case of 9), confirming their electronic structure with a S = 1 spin ground state and a high triplet-quintet energy separation. IRPD spectroscopy showed a decrease of the Fe=O stretching frequency going from 6 to 8/9, supporting the increasing axial donation. Similar findings were obtained for the peripheral methylated as well as non-methylated complexes, so that the peripheral substitution is expected to only slightly influence the electronic configuration of the oxidoiron(IV) unit. Due to the large triplet-quintet energy separation, influences from two-state reactivity can be neglected for the tetracarbene system and therefore, the axial and equatorial ligand effects on hydrogen atom abstraction (HAA) were disentangled by using substrates with weak C−H bonds (1,4- cyclohexadiene (CHD), 9,10-dihydroanthracene (DHA)/ deuterated DHA, 9H-xanthene and 10-methyl-9,10-dihydroacridine (AcrH2)). UV/Vis monitoring of the reaction in pseudo-first order conditions at different temperatures yielded kinetic traces, from whose Eyring activation parameters and Bell-Evans-Polanyi type correlations were derived. Interestingly, the presence of strong axial donors decreased the reaction rates compared to 6, in line with an electrophilic trend. Temperature-dependent kinetic isotope effect (KIE) studies and calculations underlined a special role of thiolato-coordinated complexes 8 and 9 due to increased tunnelling, therefore showing faster rates than complex 7. Peripheral methylation of the complexes slowed down all rates, again in line with an electrophilic trend for HAA.
Additionally, the reactivity of the different bis(acetonitrile)iron(II) complexes 1 towards dioxygen as an abundant natural oxidant was studied. This is of great interest since dioxygen is readily available and natural enzymes are using it as an oxidizing agent during their catalytic cycles forming different high-valent intermediates. Therefore, the replacement of artificial oxidizing agents like sPhIO (2 (tert butylsulfonyl)iodosobenzene) by sustainable ones is one goal in the field of catalysis by high-valent oxidoiron complexes to obtain greener reaction conditions. At room temperature, complexes μ-oxidodiiron(III) complexes 12 were obtained and characterized. Both μ-oxidodiiron(III) complexes 12-16H and 12-16Me were spectroscopically analyzed and showed similar features in UV-Vis, Mössbauer and Raman spectroscopy. Raman spectroscopic analyses of all μ-oxidodiiron(III) complexes of the series 12 suggested an unusual dependence of the stretching bands on the Fe–O–Fe angles. In scrambling experiments using 12-16H and 12-16Me, a mixed complex 12-16H/Me was obtained, likely due a disproportionation equilibrium forming bis(acetonitrile)iron(II) complex 1-16Me and oxidoiron(IV) complex 6-16Me. This equilibrium can explain a range of different reactivities: 12-16Me can undergo two-electron OAT reactions with phospines as well as HAA reactions with DHA due to the involvement of the oxidoiron(IV) complex.2026-04-2
Flexibility and optimization of neural codes in primate sensory cortex
No full textFlexibility and efficiency are core characteristics of any intelligent system. We have a remarkable capacity to continually learn from the structure in the world, predict upcoming situations and flexibly respond in a context-dependent manner. These mental operations build upon the structured and rich representations of the external world which exist in the sensory cortex of the brain. But flexibility is attributed to higher association cortex – implying that stability and flexibility exists in different parts of the brain. In this thesis, I challenge this notion. I first ask how efficient and flexible neural codes for perception arise in the sensory cortex through learnt priors and predictions. To this end, I conduct functional magnetic resonance imaging in the macaque monkey face-processing system, a dedicated sensory hierarchy in the primate brain. I find that top-down predictions dynamically transform neural representations in sensory cortex enabling separable, robust and abstract neural codes for perception. This provides evidence that predictions by means of feedback pathways allow cortical processing hierarchies to achieve their computational goal in an efficient manner. If indeed the sensory cortex can flexibly and efficiently achieve its computational goals, how does it also achieve flexibility when faced with multiple task-demands? I investigate this using invasive electrophysiology in human epilepsy patients that flexibly perform multiple tasks and improve their task performance over repetitions. I test the idea whether the brain adopts the strategy of re-using multipurpose shared resources for multiple tasks that can enable rapid learning and generalization. Or instead utilizes a specialized neural strategy, where different tasks are optimized in different areas, providing lesser interference. I find that the sensory neural codes in temporal cortex exhibit flexible optimization for all the tasks – something that is traditionally ascribed only to the shared resources in the frontoparietal network. Further, I find that a network-level flexibility arises whereby the flexible optimization of sensory codes is accompanied by different parts of the frontoparietal network based on task demands - hence bringing about robustness through distributed computations. Therefore, I provide evidence that flexibility is a multiscale phenomenon that efficiently makes use of the different resources available in the brain, within sensory processing hierarchies in the temporal cortex and beyond. With this, I propose that flexibility of the sensory cortex is a special ‘structured’ kind of flexibility that efficiently makes use of the information from the external world and is complementary to the flexibility afforded by the association areas.2026-06-1