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Cross-National Analysis of IVF Registry Data
No full textApproximately 15% (1 in 6) of couples worldwide face infertility issues, and assisted reproductive technology (ART), which is now adopted globally, has become a key method to address these challenges. Various in-vitro fertilization (IVF) registries across different countries and regions have provided various valuable data for research and clinical practice, which might also offer important insights for the development of artificial intelligence (AI) models. However, variations in terminology and definitions present difficulties and challenges to cross-country data comparison and the future application of AI. In addition, given that IVF clinical treatment is divided into 4 steps, different registries may focus on different steps, such as medical history and demographic information (step 1), while others place more emphasis on laboratory procedures related to ART treatment (step 2). These differences, both in quantity and content, further increase the complexity of unifying the data. This raises the questions: How can these terminology and definitions be unified, generating a standardized IVF glossary? What are the specific differences among different registries across countries and regions? And is there sufficient data or information available to support AI model development?
We selected 7 IVF registries encompassing 4 continents: the Deutsches IVF-Register (DIR) in Germany, the Society for Assisted Reproductive Technology (SART) and the Centers for Disease Control and Prevention (CDC) in the United States, the Assisted Reproductive Technology Database (ANZARD) in Australia and New Zealand, the Chinese Society of Reproductive Medicine (CSRM) in China, the European IVF Monitoring Consortium (EIM), and the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). We then systematically extracted and standardized the terminology (variables) and definitions included in each registry to ensure comparability. These variables were categorized into 4 steps according to the clinical treatment process: step 1 (patient properties before stimulation), step 2 (stimulation protocol and monitoring), step 3 (laboratory procedures), and step 4 (ART outcomes). We applied one-way ANOVA to compare the number and proportion of variables across the different steps to assess whether significant differences exist between them. We also used statistical models to fit the data and identify underlying patterns. Besides, we studied sub-grouping and combinations of variables, and, used network diagrams to visualize the relationships between variables to reveal the frequency and patterns of variable usage across the different registries.
A standardized IVF glossary containing a total of 196 terms as variables and their definitions was generated from 7 selected IVF registries. The estimated maximum number of variables, derived through model fitting, was approximately 330, with DIR containing the largest number of variables, accounting for less than 1/3 of the estimated total (97 variables), and ICMART containing the fewest, less than 10% (24 variables).
Summary 59
The 3 most frequently used variables were age, ET (embryo transfer), and CP (clinical pregnancy). The average proportion of variables in each step was as follows: step 1 (36%), step 2 (2%), step 3 (40%), and step 4 (21%). The proportion in step 2 differed significantly from the other steps (P 2). The distribution of sub-grouped variables followed a generalized gamma distribution, however, not belong to any recognized distribution sub-family. And step 2 showed a significant difference from step 1 (P<0.05, one way ANOVA) in terms of the average occurrence of the variables. In the analysis of variable combinations, the range of combined correlated variables varied from 2 to 8. DIR had the most combinations (471) and significant difference (P < 0.05, one-way ANOVA), while ICMART had the fewest (43). Among these, combinations involving 3 and 4 variables were the most common, with 231 and 272 combinations, respectively. Additionally, we found that the frequency of variable usage, the overall connections between variables, and the number of unique connections for each variable followed Weibull distributions. Finally, we analyzed the most common variable pairs across the 7 registries, and the most frequent pairs were year- prospectivity (DIR), age-autologous (SART), age-autologous (CDC), autologous-fresh cycle (ANZARD), year-ET (CSRM), country-delivery (EIM), and autologous-delivery (ICMART).
This study underscores the importance of standardizing IVF data, which is critical for enhancing cross-national comparability and enabling more comprehensive analyses. Significant differences in the quantity of variables and data collection across registries were identified, particularly in step 2 (involving stimulation protocols and monitoring), where the data are notably sparse and, in some cases, missing. This inadequacy fails to sufficiently reflect the complexity of clinical decisions and interventions in this stage. Furthermore, the number of variables within each registry, and across all registries, falls far short of the estimated maximum variable count of 330, derived through model fitting. Although the standardized data are not yet ready for direct application in AI models, they provide a valuable foundation for AI model development. We also propose the inclusion of key variables at different stages of treatment, such as lifestyle factors, medication details and response, embryo grading, and transfer procedures, to improve the comprehensiveness of the data, which also could link to the weights in AI model development. Our analysis further revealed that variable distributions conform to some interesting statistical distribution sub-families, highlighting the complexity and inherent randomness in the data and the network diagrams illustrate structural differences in data usage across registries, supporting future efforts in data integration and optimization. Finally, we propose a Generative Adversarial Network-based AI model to generate personalized stimulation protocols, facilitating the optimization of assisted reproductive treatments.2026-06-0
Uncovering the interactome of peripheral myelin protein 22 kDa (PMP22) to understand its role in health and neuropathy
No full textPMP22, a hydrophobic glycoprotein, is crucial for proper myelination in Schwann cells of the peripheral nervous system. Dosage alterations lead to the neuropathies Charcot-Marie-Tooth disease 1A (CMT1A), where PMP22 is overexpressed, resulting in hypomyelination of medium to large caliber axons, and hereditary neuropathy with liability to pressure palsies (HNPP) with focal hypermyelination due to PMP22 haploinsufficiency. While the pathological consequences of PMP22 mutations are well documented, their molecular effect, i.e. the mechanisms of PMP22 (dys)function, remain poorly understood. One possible explanation for this shortcoming is the limited knowledge about protein-protein interactions that may mediate the cellular function(s) of PMP22. In this study, I investigated PMP22’s protein-protein interactions across various cellular systems, including HEK293T, MDCKII, and primary Schwann cells, using highly stringent Co-immunoprecipitation coupled with mass spectrometric analysis. A comprehensive interactome was generated, validating existing proposed interactions in fundamental cellular processes with partners such as calnexin, LMAN2, and STIM1, as well as interactions that specifically occur in Schwann cells, such as myelin protein zero. In addition to the existing body of 124 direct or indirect interacting proteins of PMP22 I identified 577 novel candidates with proteins involved in cell adhesion, signaling, and lipid metabolism. A key focus of my study was the interaction between PMP22 and caveolin-1 (CAV1), the signature protein of caveolae, which in myelinating Schwann cells is found in non-compact myelin regions. I could validate their interaction biochemically and demonstrate their immediate proximity in the cell. In the peripheral nerve, the compact myelin protein PMP22 and CAV1 were shown via immune electron microscopy to coexist in plasma membrane caveolae and possibly caveolae at the outermost myelin layer. I also found that PMP22 overexpression had a major impact on CAV1/caveolae in Schwann cells, demonstrating a strong functional connection between these proteins. CAV1 protein expression initially increased upon PMP22 overexpression in CMT1A. However, protein levels normalized during development, while numbers of plasma-membrane-bound caveolae were substantially decreased in Schwann cells of CMT1A rats during developmental myelination and in adulthood. Intriguingly, animals showing a severe disease phenotype had less caveolae than mildly affected animals, indicating an involvement of caveolae in CMT1A pathogenesis. Cav1 knockout mice have been reported to suffer from neurological deficits, however, it is still unclear to what extent central or peripheral functions are affected. Electron microscopy showed that loss of Cav1 results in hypomyelination of peripheral axons in adult mice. At the same time, its overexpression in Schwann cells in co-cultures with neurons also resulted in a myelination defect, highlighting the need for correct CAV1 dosage for proper peripheral nerve myelination. Collectively, my data suggest that CAV1 is necessary for normal peripheral myelination and further provide evidence for an involvement of CAV1–through interaction with the disease-causing protein PMP22–in CMT1A pathogenesis.
Finally, I investigated the actin cytoskeleton in CMT1A rats, where I hypothesized a functional role of PMP22 through its novel interaction with LIM domain kinase 2 (LIMK2), an important regulator of the actin-severing protein cofilin. CMT1A sciatic nerves showed a significant reduction in filamentous actin, in line with increased cofilin activation as evidenced by a reduction in protein phosphorylation. Schmidt-Lanterman incisures, which are highly enriched in actin filaments, are significantly affected by this loss.
The work presented in this thesis identifies novel PMP22-interacting proteins that may contribute to PMP22’s role in peripheral nerve (dys)myelination, with a specific focus on CAV1.2026-05-0
Funktionelle Charakterisierung des organischen-Kationen Protonen Antiporters (H+/OC) und der Kationentransporter MATE1, MATE2-K, OCT1, OCT2, OCT3 und PMAT
No full textEtwa 30 % aller endogenen Substanzen sowie vieler Medikamente und anderer biologisch relevanter Moleküle gehören zu den organischen Kationen. Ein zentrales Forschungsinteresse dieser Arbeit war, zu untersuchen, wie diese positiv geladenen Moleküle biologische Barrieren, insbesondere die Blut-Hirn-Schranke (BBB), überwinden. Im Fokus stand der H⁺/organische Kationen (H⁺/OC)-Antiporter, der in Endothelzellen des Gehirns stark exprimiert wird, aber genetisch bislang nicht identifiziert ist. Seine Funktion wurde in der hCMEC/D3-Zelllinie untersucht. Zusätzlich wurden sechs SLC-(Solute-Carrier)-Transporter (MATE1, MATE2K, OCT1, OCT2, OCT3 und PMAT) analysiert, die vor allem den zellulären Influx und Efflux organischer Kationen in Leber und Niere vermitteln. Hierfür wurden HEK293-Zellen verwendet, die diese Transportproteine hoch exprimieren. Ziel der Arbeit war es, bislang unbekannte Substrate dieser Transporter zu identifizieren, chemische Eigenschaften vorherzusagen, die Transporter-Interaktionen bestimmen, mögliche Korrelationen zwischen Transportaktivitäten aufzuzeigen und die Transporteigenschaften den typischen Einsatzgebieten der Substanzen zuzuordnen. Neben Medikamenten wurden auch endogene Substanzen untersucht, die zukünftig als Marker für die Aktivität von Transportproteinen beim Menschen dienen könnten.Approximately 30% of all endogenous substances, as well as many drugs and other biologically relevant molecules, are organic cations. A central aim of this work was to investigate how these positively charged molecules cross biological barriers, particularly the blood-brain barrier (BBB).
The focus was on the H⁺/organic cation (H⁺/OC) antiporter, which is highly expressed in brain endothelial cells but has not yet been genetically identified. Its transport function was studied using the hCMEC/D3 cell line. In addition, six SLC (solute carrier) transporters (MATE1, MATE2K, OCT1, OCT2, OCT3, and PMAT) were analyzed, as they primarily mediate the cellular influx and efflux of organic cations in the liver and kidney. HEK293 cells overexpressing these transport proteins were used for these analyses.
The aim of this study was to identify previously unknown substrates of these transporters, predict chemical properties that determine transporter interactions, examine potential correlations between transporter activities, and relate transport profiles to the typical applications of the substances. In addition to drugs, endogenous compounds were also investigated, which may in the future serve as markers for transporter activity in humans.2026-02-0
Analysis of simultaneous RANKL-inhibition and OPG-upregulation through virus-like particle mediated RNA-interference in a rat model
No full textDie Osteoporose ist durch ein Ungleichgewicht im Knochenstoffwechsel mit Überwiegen des Knochenabbaus gekennzeichnet, wobei der RANK RANKL OPG Signalweg die Osteoklastendifferenzierung steuert. Ziel dieser Arbeit war die Etablierung einer simultanen RANKL-Inhibition und OPG-Expressionssteigerung durch virusähnliche Partikel (VLP) mit siRNA gegen RANKL und/oder OPG-DNA-Kassetten im Knochen gesunder weiblicher Ratten sowie die Untersuchung eines möglichen Retard-Effekts durch Applikation der VLP in Chitosan-Gel.
48 Ratten wurden in Kontrollgruppen (keine Injektion, VLP mit Kontroll-siRNA, VLP mit GFP-Konstrukt) und mehrere Interventionsgruppen eingeteilt, die entweder zweimal intraperitoneal VLP mit OPG-DNA Kassetten und/oder siRANKL oder einmal die mit OPG-DNA-Kassetten und/oder siRANKL beladenen VLP in Chitosan-Gel erhielten. Nach 3, 7 oder 14 Tagen wurden die Ratten getötet und die Tibiae entnommen. Die Expression von RANKL und OPG wurde mittels qRT-PCR (∆∆CT Methode, β2 Mikroglobulin als Referenzgen) sowie mittels Western Blot bestimmt. Für den Proteinnachweis wurde ein umfangreich optimiertes Western-Blot-Protokoll mit Vergleich verschiedener Lysepuffer, Transfermethoden, Antikörper und Normalisierungsstrategien entwickelt; OPG wurde stain-free basiert, RANKL nach parallelem Gel-Ansatz und Normalisierung auf die Gesamtproteinmenge quantifiziert.
Die qPCR zeigte in allen Interventionsgruppen signifikante Reduktionen der RANKL-mRNA um etwa 30–70% gegenüber den Kontrollen, mit dem stärksten Knockdown nach einmaliger Injektion von Chitosan mit VLP und siRANKL. OPG-mRNA ließ sich durch OPG-DNA-Kassetten und in mehreren Gruppen mit kombinierter Intervention zeitlich begrenzt signifikant steigern, während alleinige siRANKL-Gabe die OPG-mRNA nicht erhöhte. Auffällig war ein ausgeprägter RANKL-mRNA-Abfall auch nach alleiniger OPG-DNA-Gabe. Chitosan führte für RANKL-mRNA zu länger anhaltend niedrigen Expressionsniveaus, während sich für OPG-mRNA kein konsistenter Retard Effekt zeigte. Western Blots bestätigten deutliche OPG-Protein-Expressionssteigerungen bis über das Doppelte der Kontrollwerte, während der RANKL-Protein-Knockdown nur Zeitpunkt- und gruppenabhängig signifikant waren und insgesamt eine höhere Variabilität aufwiesen.
Die Ergebnisse belegen, dass sowohl ein VLP-vermittelter RANKL-Knockdown durch siRNA als auch eine OPG-Expressionssteigerung durch OPG-DNA-Kassetten im Rattenknochen erreichbar sind und dass OPG-DNA offenbar zusätzlich die RANKL-mRNA beeinflusst. Ein klarer additiver Effekt der simultanen Intervention auf den RANKL-Knockdown ließ sich nicht nachweisen, für OPG sprechen die Daten hingegen für einen zusätzlichen Einfluss der Kombination. Trotz intensiver methodischer Optimierung sind die Proteinbefunde durch begrenzte Tierzahl, fehlende Replikate und Antikörper-spezifische Probleme eingeschränkt interpretierbar. Im Gegensatz dazu wiesen die qPCR-Daten eine hohe methodische Qualität auf und erlauben spannende Rückschlüsse auf die komplexen Mechanismen. Insgesamt deuten die Daten auf komplexe Regulationsmechanismen im RANKL–OPG-System hin, die über eine einfache Rezeptor–Ligand-Interaktion hinausgehen.Osteoporosis is characterized by an imbalance in bone metabolism with a predominance of bone resorption, with the RANK–RANKL–OPG signaling pathway controlling osteoclast differentiation. The aim of this work was to establish simultaneous RANKL-inhibition and OPG-upregulation in the bone of healthy female rats by means of virus-like particles (VLPs) carrying siRNA against RANKL and/or OPG-DNA cassettes, as well as to investigate a possible retard-effect through application of the VLPs in chitosan-gel.
Forty-eight rats were divided into control groups (no injection, VLPs with control-siRNA, VLPs with a GFP-construct) and several intervention groups that received either two intraperitoneal injections of VLPs with OPG-DNA cassettes and/or siRANKL within 7 days, or a single injection of chitosan-gel containing VLPs loaded with OPG-DNA cassettes and/or siRANKL. After 3, 7, or 14 days, the rats were sacrificed and the tibiae were collected. RANKL and OPG expression was determined by qRT-PCR (∆∆CT-method, β2-microglobulin as reference gene) and by Western blot. For protein detection, an extensively optimized Western blot protocol was developed, including comparison of different lysis buffers, transfer methods, antibodies, and normalization strategies; OPG was quantified using a stain-free based approach, and RANKL was quantified after a parallel gel run with normalization to total protein content.
qPCR revealed significant reductions in RANKL-mRNA of approximately 30–70% compared with controls in all intervention groups, with the strongest knockdown after a single injection of chitosan containing VLPs and siRANKL. OPG-mRNA was significantly increased in a time-limited manner by OPG-DNA cassettes and in several groups with combined interventions, whereas siRANKL alone did not increase OPG-mRNA. A pronounced decrease in RANKL-mRNA was also observed after administration of OPG-DNA alone. Chitosan led to more prolonged low expression levels of RANKL-mRNA, while no consistent retard-effect was seen for OPG-mRNA. Western blots confirmed marked increases in OPG-protein levels to more than twice the control values, whereas reductions in RANKL-protein were only significant depending on time point and group and showed overall higher variability.
The results demonstrate that both a VLP-mediated RANKL-knockdown by siRNA and an OPG-upregulation by OPG-DNA cassettes can be achieved in rat bone and that OPG-DNA apparently also influences RANKL-mRNA. A clear additive effect of the simultaneous intervention on the RANKL-knockdown could not be demonstrated, whereas the data for OPG indicate an additional effect of the combination. Despite intensive methodological optimization, interpretation of the protein data is limited by the small number of animals, lack of replicates, and antibody-specific issues. In contrast, the qPCR data exhibited high methodological quality and allow intriguing insights into the complex regulatory mechanisms in the RANKL–OPG system that extend beyond simple receptor–ligand interaction.2026-02-1
3d Transition Metal-Catalyzed C–H Activation for Late-Stage Functionalization
No full textTransition metal-catalyzed direct C–H activation has become a versatile platform for highly efficient and selective molecular transformations. Specifically, 3d transition metal catalysts, which are more earth-abundant and cost-effective, have attracted major attention as a sustainable approach. Additionally, integrating electrosynthesis and C–H functionalization has enabled resource-economical strategies for the construction of C–C and C–Het bonds. In this thesis, several distinct transformations with 3d transition metals and/or electrochemistry were developed, and especially, the late-stage functionalization of structurally complex peptides and drug molecules was investigated.2026-11-2
Untersuchung der Plastizitätsveränderung im Motorcortex durch Manipulation der Direktionalität und Pulsbreite bei hochfrequenter transkranieller Magnetstimulation mit einem cTMS-Gerät: Eine mehrfaktorielle Varianzanalyse
No full textThis work investigates how the directionality and pulse width of high‑frequency cTMS pulses influence plasticity in the human motor cortex. In a 10‑Hz rTMS study with 15 healthy participants, four cTMS pulse types were tested in a repeated‑measures design, with RMT and normalized MEP amplitudes analyzed using rmANOVA. Longer pulses showed lower RMT values, and there were significant main effects of pulse width and directionality on RMT as well as a significant three‑way interaction (directionality×pulse width×time) on MEP after‑effects, indicating parameter‑dependent modulation of motor plasticity by cTMS.2026-03-0
Dissecting STRIPAK-mediated signaling pathways in the ascomycete Sordaria macrospora using proximity-dependent Biotin Identification
No full textDer filamentöse Ascomycet Sordaria macrospora (Sm) dient als Modellorganismus zur Untersuchung der Fruchtkörperentwicklung, um die grundlegenden Prozesse der multizellulären Entwicklung in Eukaryoten aufzudecken. Ein zentraler Regulator dieses Prozesses in S. macrospora ist der Striatin-interagierende Phosphatase- und Kinase-Komplex (SmSTRIPAK). Dieser Multiproteinkomplex ist von Pilzen bis zu Tieren konserviert und fungiert als zentraler Knotenpunkt in der Signaltransduktion, der verschiedene Entwicklungsprogramme durch präzise Phosphorylierung und Dephosphorylierung seiner Zielproteine koordiniert. Dabei geht der SmSTRIPAK-Komplex vorübergehend eine Protein-Protein-Interaktion mit seinen Substraten ein. Die Substrate werden entweder durch seine aktive Phosphatase dephosphoryliert oder durch die rekrutierten Kinasen phosphoryliert. Trotz umfangreicher Forschung ist das zugrunde liegende dynamische Protein-Protein-Interaktionsnetzwerk des SmSTRIPAK-Komplexes noch nicht vollständig aufgeklärt.
Um diese Lücke zu schließen, wurde in dieser Arbeit die Biotin-Identifikationsmethode (BioID) zur proximitätsabhängigen Markierung in S. macrospora unter Verwendung der SmSTRIPAK-Komplex-Interaktor 1 Untereinheit (SCI1) etabliert, um mögliche Substrate des SmSTRIPAK-Komplexes zu identifizieren. Anfangs wurde die TurboID Biotin Ligase für die Markierung benachbarter Proteine verwendet, aber die Methodik wurde durch die Verwendung einer kleineren Ligase-Variante namens miniTurboID erweitert. Durch verschiedene Kontrollen und globale Proteomanalysen von Zellextrakten konnten wir mittels Massenspektrometrie eine signifikante Anreicherung zahlreicher mutmaßlicher Interaktoren des SmSTRIPAK Komplexes aufdecken. Diese Kandidaten zeigen eine deutliche Überschneidung mit Datensätzen aus vorherigen Co-Immunpräzipitations-, Transkriptom- und Proteom-Experimenten, was unseren Ansatz zur Erfassung biologisch relevanter Interaktionen mittels BioID validiert.
Die resultierenden Proxiom-Daten unterstreichen die Rolle des SmSTRIPAKs als zentralen Knotenpunkt in der Signaltransduktion während der Pilzentwicklung. Die Daten liefern in vivo Evidenz für die Kolokalisierung des SmSTRIPAK Komplexes mit Proteinen aus anderen konservierten Pilz-Signaltransduktionswegen, darunter das Septationsinitiierungs-netzwerk (SIN), die MAPK-Kaskade des Pheromonsignalwegs (PR), und die Ribosomenbiogenese. Darüber hinaus identifizierten wir das Greenbeard-Protein SmDOC2 als mutmaßlichen SmSTRIPAK-Interaktor. Zur genaueren Untersuchung der Smdoc-Gene in S. macrospora haben wir Deletionsmutanten erzeugt und deren Phänotypen charakterisiert. Die Einzel-Deletionsstämme ΔSmdoc1 und ΔSmdoc2 wiesen schwere Defekte in der Fruchtkörperentwicklung auf, während der Doppel-Deletionsstamm ΔSmdoc1ΔSmdoc2 eine wildtyp-ähnliche Fertilität aufweist. Unsere kombinierten Ergebnisse aus TurboID-basierten BioID Experimenten, Hefe-Zwei-Hybrid Assays und Fluoreszenzmikroskopie mit SmDOC1 und SmDOC2 weisen auf eine enge funktionelle Verbindung der SmDOC Proteine mit Komponenten des PR-Signalwegs hin. Zusammengefasst ergeben diese Ergebnisse ein Modell, in dem die DOC1/2-Proteine einen neuartigen regulatorischen Knotenpunkt bilden, der möglicherweise den STRIPAK Komplex mit dem PR-MAPK-Signalweg während der Pilzentwicklung verbindet.The filamentous ascomycete Sordaria macrospora (Sm) serves as a model to study fruiting body development with the aim of uncovering the fundamental processes that shape the differentiation of multicellular eukaryotic life. A central regulator of this process in S. macrospora is the striatin-interacting phosphatase and kinase (SmSTRIPAK) complex. This multiprotein assembly is conserved from fungi to animals and functions as a key signaling hub that coordinates developmental programs by the precise phosphorylation and dephosphorylation of its target proteins. Therefore, the SmSTRIPAK complex transiently recruits substrates to its catalytic phosphatase core or to complex-associated kinases. Despite extensive research, the underlying dynamic protein-protein interaction network of the SmSTRIPAK complex remains incompletely resolved.
To address this gap, this work established the biotin identification (BioID) proximity labeling method in S. macrospora using the STRIPAK complex interactor 1 (SCI1) subunit of the complex and screened for putative target proteins of the SmSTRIPAK complex. Initially, the TurboID biotin ligase was used for proximity labeling of nearby proteins, but the methodology was extended by adopting a smaller ligase variant named miniTurboID. Using rigorous controls and global proteome analyses of whole-cell lysates, we discovered that numerous putative SmSTRIPAK complex interactors were significantly enriched in the mass spectrometry data. These candidates substantially overlap with prior co-immunoprecipitation, transcriptomic and proteomic datasets, thus validating our approach to capture biologically relevant interactions with BioID.
The resulting proxiome data highlights the SmSTRIPAK’s central role as a signaling hub in fungal development and provides in vivo evidence for its co-localization with components of other conserved fungal signaling pathways, including the septation initiation network (SIN), the pheromone response (PR) MAPK cascade and ribosome biogenesis. The proximity data also implicated the greenbeard protein SmDOC2 as a putative SmSTRIPAK interactor. For closer investigation of the Smdoc genes in S. macrospora, we generated null mutant strains, performed complementation experiments and phenotypic analyses. The single deletion strains ΔSmdoc1 and ΔSmdoc2 exhibited severe defects in fruiting body development, whereas the double deletion strain ΔSmdoc1ΔSmdoc2 retained wild-type like fertility. Our combined data from TurboID-based proximity mapping, yeast two-hybrid assays and fluorescence microscopy with SmDOC1 and SmDOC2 indicate a tight functional association with components of the PR signaling pathway. Together, these findings converge on a model in which the DOC1/2 proteins constitute a novel regulatory circuit that might link STRIPAK signaling with the PR MAPK signaling pathway during fungal development.2026-01-2
Development of lipid-based biomarkers for the activity and progression of Multiple Sclerosis
No full textThis study investigates the potential of plasma lipidomic profiles to support the diagnosis of Multiple Sclerosis (MS) and to distinguish between clinical disease courses. Plasma samples from 60 patients with MS, classified as relapsing–remitting (RRMS) or chronic progressive MS (CPMS), and 60 age-matched controls were analyzed using direct-infusion quantitative shotgun lipidomics. Lipid data were adjusted for age and body mass index to reduce confounding effects. Multivariate analyses, including principal component analysis, orthogonal partial least squares discriminant analysis, and random forest modeling, were applied, complemented by a class composition visualization to assess lipid class–level changes. A total of 670 lipid species across 16 classes were identified. Patients with MS showed increased diacylglycerol levels, with DAG 16:0;0_18:1;0 demonstrating the highest predictive value for MS. Alterations in phosphatidylethanolamines were mainly associated with RRMS, whereas ether-linked phosphatidylethanolamines characterized CPMS. Additionally, cholesteryl esters were reduced in CPMS, while triacylglycerols were decreased in RRMS. Overall, distinct plasma lipidomic signatures were identified that correlate with specific MS disease courses, highlighting their potential utility for improved disease stratification and personalized therapeutic approaches.2026-03-1
Logenabszesse in der Mund-, Kiefer- und Gesichtschirurgie - eine retrospektive Analyse
No full textHintergrund:
Logenabszesse im Kopf- und Halsbereich stellen trotz moderner antibiotischer und chirurgischer Therapie weiterhin potenziell lebensbedrohliche Erkrankungen dar. Aufgrund der komplexen Anatomie und möglicher schwerer Komplikationen wie Atemwegsobstruktion, Mediastinitis oder Sepsis ist eine frühzeitige Diagnostik und konsequente Therapie essenziell.
Ziel der Arbeit:
Ziel dieser retrospektiven Studie war es, die Ätiologie, klinischen Verläufe, diagnostischen Verfahren, mikrobiologischen Befunde, Therapie und Komplikationen von Patienten mit Logenabszessen in der Mund-, Kiefer- und Gesichtschirurgie zu analysieren sowie relevante Risikofaktoren zu identifizieren.
Material und Methoden:
Untersucht wurden 249 Patienten, die im Zeitraum von 01.01.2010 bis 01.01.2021 an der Klinik für Mund-, Kiefer- und Gesichtschirurgie der Universitätsmedizin Göttingen stationär behandelt wurden. Die Datenerhebung erfolgte retrospektiv anhand definierter ICD-Codes. Erfasst wurden demografische Daten, Abszesslokalisation, Ätiologie, Komorbiditäten, Laborparameter, bildgebende Verfahren, mikrobiologische Befunde, Therapie und Komplikationen. Die statistische Auswertung erfolgte mittels Mann-Whitney-U- und Chi-Quadrat-Test.
Ergebnisse:
Das durchschnittliche Alter der Patienten betrug 49,6 Jahre bei nahezu gleicher Geschlechterverteilung. Die häufigste Abszesslokalisation war das Spatium peri- und paramandibulare. In 84,3 % der Fälle lag eine odontogene Ursache vor, insbesondere im Bereich der Unterkiefermolarregion. Patienten mit multiplem Logenbefall zeigten signifikant höhere CRP-Werte und eine signifikant längere stationäre Aufenthaltsdauer. Mikrobiologisch dominierten polymikrobielle Infektionen mit Erregern der oralen Mischflora, vor allem Streptococcus-Spezies.
Schlussfolgerung:
Logenabszesse sind weiterhin überwiegend odontogenen Ursprungs. Eine frühzeitige Diagnostik, konsequente chirurgische Therapie und interdisziplinäre Betreuung sind entscheidend, insbesondere bei Patienten mit ausgedehntem Logenbefall.Background:
Deep neck space abscesses remain potentially life-threatening conditions despite advances in antibiotic and surgical treatment. Due to the complex anatomy of the head and neck region and the risk of severe complications such as airway obstruction, mediastinitis, or sepsis, early diagnosis and prompt therapy are essential.
Objective:
The aim of this retrospective study was to analyze the etiology, clinical course, diagnostic procedures, microbiological findings, treatment, and complications of patients with deep neck space abscesses in oral and maxillofacial surgery, and to identify relevant risk factors.
Materials and Methods:
A total of 249 patients treated as inpatients for deep neck space abscesses at the Department of Oral and Maxillofacial Surgery, University Medical Center Göttingen, between January 1, 2010 and January 1, 2021 were retrospectively analyzed. Patient selection was based on defined ICD codes. Data collected included demographic information, abscess localization, etiology, comorbidities, laboratory parameters, imaging modalities, microbiological findings, treatment, and complications. Statistical analysis was performed using the Mann–Whitney U test and the chi-square test.
Results:
The mean age of patients was 49.6 years with an almost equal gender distribution. The most common abscess localization was the peri- and paramandibular space. Odontogenic infection was identified as the cause in 84.3% of cases, most frequently originating from the mandibular molar region. Patients with multiple space involvement showed significantly higher C-reactive protein levels and a significantly longer hospital stay. Microbiological analysis revealed predominantly polymicrobial infections with organisms of the oral flora, mainly Streptococcus species.
Conclusion:
Deep neck space abscesses are still predominantly of odontogenic origin. Early diagnosis, prompt surgical intervention, and interdisciplinary management are crucial, particularly in patients with extensive space involvement.2026-04-1
Gold Nanostar-Based Core–Satellite Nanotags for Surface-Enhanced Resonance Raman Spectroscopy
No full textSurface-enhanced Raman scattering (SERS) nanotags based on plasmonic nanostructures have emerged as powerful tools for ultrasensitive bioanalytical detection. Rational synthesis of SERS nanotags with high sensitivity and efficiency remains critical for achieving reproducible quantitative detection and real-world implementation.
This thesis presents the systematic development of NIR-compatible gold nanostar (AuNS)-based core--satellite nanostructures engineered for ultrasensitive SERS detection.
Starting from AuNSs as the core component, we explored the effects of different parameters on AuNS morphology, particle size distribution, and optical response under up-scaled synthetic conditions, achieving precise LSPR tuning to match the laser excitation wavelength at 785 nm. 4-arm star polymers synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization served as dual-functional stabilizing agents and interparticle linkers, with shorter chain lengths providing morphological stability while maintaining colloidal dispersibility. Under NIR laser irradiation, AuNS@PNIPAM displayed good photothermal performance with excellent stability.
Subsequently, a strategy was developed to maximize the SERS signal of individual nanotags through rational structural design in which satellites were utilized to create additional electromagnetic hot spots and 3D loading of reporter molecules was enabled. Using 4-arm polymers as interparticle linkers, exceptionally high satellite loading of approximately 35 satellites per core was achieved, with tunable interparticle distances controlled by varying the chain length of linear spacer polymers. A polyelectrolyte-assisted deposition strategy was employed to incorporate resonant dyes lacking anchoring points as reporter molecules, enabling 3D reporter loading that transcended traditional monolayer limitations.
Finally, SERS performance was evaluated through systematic measurements. Using confocal Raman microscopy, dramatic signal enhancement under in-resonance excitation compared to off-resonance conditions was observed. Peak assignment confirmed that all major Raman signals were exclusively attributed to the reporter molecules. In liquid-phase measurements, a satellite-free reference sample was designed, and through normalization of reporter molecule content, the specific contribution of satellites to SERS enhancement was isolated. Core--satellite samples exhibiting balanced plasmonic coupling and hot spot accessibility demonstrated up to 4-fold signal amplification compared to satellite-free references. Excellent linearity with concentration was observed across all samples, with the optimized formulation achieving a detection limit of 10 femtomolar. The results demonstrate that rationally designed hierarchical nanostructures enable highly sensitive and robust SERS detection, establishing a versatile platform for advanced bioanalytical applications.2026-12-1