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Terrestrial Carbon Dynamics under Land Use Transformation in Jambi, Indonesia
Get PDFIndonesia Endowment Fund for Education (LPDP)Tropische Wälder in Indonesien werden großflächig in landwirtschaftliche Systeme umgewandelt, insbesondere in Ölpalmen- und Kautschukplantagen. Diese Umwandlungen verändern die Kohlenstoffdynamik erheblich, was zu starken Verlusten bei der terrestrischen Kohlenstoffspeicherung und erhöhten CO2-Emissionen führt. Der Klimawandel verschärft diese Auswirkungen, indem er die Temperatur- und Niederschlagsmuster verändert und häufigere extreme Wetterereignisse auslöst. Trotz ihrer tiefgreifenden Auswirkungen auf den terrestrischen Kohlenstoffkreislauf sind die langfristigen Folgen dieser kombinierten Faktoren nach wie vor nur unzureichend bekannt. Daher habe ich das Community Land Model Version 5 (CLM5) eingesetzt, um die langfristigen Auswirkungen von Landnutzungsänderung und Klimawandel auf die Kohlenstoffvorräte und -flüsse in Jambi, Indonesien, zu simulieren. Diese Simulationen umfassen Szenarien mit mehreren Fruchtfolgen von Ölpalmen und Kautschuk, Wiederaufforstung und Klimawandel
Bevor das Modell zur Vorhersage der langfristigen Auswirkungen genutzt wurde, habe ich zunächst die Parametrisierung für tropischen Regenwald innerhalb von CLM5 kalibriert, um die Kohlenstoffdynamik am Untersuchungsort Jambi besser zu simulieren. Dabei wurden die wichtigsten Modellparameter, die für den Kohlenstoffkreislauf der Vegetation relevant sind, angepasst. Die Parameter für Erhaltungsatmung und Kohlenstoffallokation erwiesen sich als entscheidend für die Verbesserung der Modellleistung. Diese Kalibrierung reduzierte die Unsicherheiten bei der Simulation der Nettoprimärproduktivität (NPP) und der Biomasse im Jambi-Wald. Darüber hinaus zeigte das kalibrierte Modell eine verbesserte Leistung an unabhängigen Standorten in Südostasien.
Mit dem kalibrierten Modell habe ich die langfristigen Auswirkungen der Umwandlung von Wäldern in Ölpalmen- und Kautschukplantagen untersucht, einschließlich mehrerer Rotationszyklen und der Erholungszeiten bei der Rückumwandlung in Wälder. Die Ergebnisse zeigen, dass die Umwandlung von Wäldern in Ölpalmen die Gesamtkohlenstoffvorräte um 59 % verringert, während die Umwandlung in Kautschukplantagen zu einem Verlust von 49 % führt. Nachfolgende Rotationszyklen verschärfen den Kohlenstoffabbau, wobei Kautschukplantagen während des zweiten Zyklus 12 % des Kohlenstoffs verlieren. Die Wiederaufforstung
nach der Nutzung als Plantage bietet Potenzial zur Kohlenstoffrückgewinnung, wobei der organische Bodenkohlenstoff (SOC) nach 69 bis 93 Jahren das Niveau vor der Umwandlung erreicht, abhängig von der vorherigen Landnutzung und den Rotationszyklen.
Zusätzlich habe ich die Kohlenstoffdynamik unter einem Klimaszenario mit hohen Emissionen (RCP8.5) untersucht. Die Ergebnisse zeigen, dass Kohlenstoffvorräte und Produktivität in Wäldern und Ölpalmenplantagen unter dem RCP8.5-Szenario deutlich abnehmen. In Ölpalmenplantagen sinken die Kohlenstoffvorräte und -flüsse um bis zu 30 %, 20 % bzw. 60 % bei Biomasse-C, organischem Bodenkohlenstoff (SOC) und Nettoprimärproduktivität (NPP). Wälder weisen eine verringerte NPP und einen Netto-Ökosystem-Austausch (NEE) von nahezu Null auf, was auf ein vermindertes Kohlenstoffbindungspotenzial hindeutet. Kautschukplantagen zeigen eine gemischte Reaktion, mit einem leichten Rückgang des Kohlenstoffs in der Biomasse, aber einem Anstieg des SOC. Landnutzungsänderung alleine verringert die Kohlenstoffspeicherung bereits erheblich, aber in Kombination mit dem Klimawandel werden diese Auswirkungen noch verstärkt. Bei der Wiederaufforstung sind die Erholungsraten unter RCP8.5 schneller, da mehr Streu anfällt und der Kohlenstoffkreislauf beschleunigt wird.
Diese Forschungsarbeit stellt eine verbesserte Parametrisierung von tropischen Regenwäldern innerhalb des CLM5-Modells vor, die zur Simulation von Kohlenstoffvorräten und -flüssen in Südostasien genutzt werden kann. Darüber hinaus liefert sie wertvolle langfristige Erkenntnisse über die Auswirkungen der Umwandlung von Wäldern in Ölpalmen- und Kautschukplantagen und die Widerstandsfähigkeit dieser Landnutzungen gegenüber dem Klimawandel.Tropical forests in Indonesia are rapidly being converted into agricultural systems, particularly oil palm and rubber plantations. These transformations significantly alter carbon dynamics, leading to substantial losses in terrestrial carbon storage and increased CO2 emissions. Climate change further exacerbates these effects by altering temperature and precipitation patterns and by triggering more frequent extreme weather events. Despite their profound implications on terrestrial carbon cycle, the long-term effects of these combined drivers remain poorly understood. Therefore, I utilized the Community Land Model version 5 (CLM5) to simulate their long-term impacts on carbon stocks and fluxes in Jambi, Indonesia. This simulation includes scenarios of multiple rotations of oil palm and rubber, reforestation, and climate change.
Before employing the model to predict long-term impacts, I first calibrated the tropical forest plant functional type (PFT) parameterization within CLM5 to better simulate carbon dynamics in the study site, Jambi. Calibration of key model parameters associated with carbon dynamics in vegetation was conducted. Parameters related to maintenance respiration rates and carbon allocation were identified as the most critical for improving model performance. This calibration reduced errors in net primary productivity (NPP) and biomass predictions in the Jambi forest. Additionally, the calibrated model demonstrated improved performance across independent sites in Southeast Asian.
Using the calibrated model, I explored the long-term impacts of converting forests into oil palm and rubber plantations, including multiple rotation cycles and recovery times when converted back to forests. Results reveal that forest-to-oil palm conversion reduces total carbon stocks by 59%, while forest-to-rubber conversion results in a 49% loss. Subsequent rotation cycles exacerbate carbon depletion, with rubber and oil palm plantations losing 12%, 1% more of carbon during the second cycle, respectively. Reforestation following plantation use offers potential for carbon recovery, with soil organic carbon (SOC) reaching pre-conversion levels after 69–93 years, depending on previous land-use types and rotation cycles.
Additionally, I examined carbon dynamics under a high-emission climate scenario (RCP8.5). Results indicate that carbon stocks and productivity are projected to be significantly reduced in the forest and oil palm under the RCP8.5 scenario. Oil palm
plantations would decreases in carbon stocks and fluxes, with reductions of up to 30%, 20%, and 60% in biomass carbon (C), soil organic carbon (SOC), and net primary productivity (NPP), respectively. Forests exhibit reduced NPP and near-zero net ecosystem exchange (NEE), suggesting diminished carbon sequestration potential. Rubber plantations show a mixed response, with a slight decrease in biomass carbon but an increase in SOC. Furthermore, land-use change alone significantly decreases carbon storage, but combined with climate change, these impacts are amplified. When reforested, recovery rates are faster under RCP8.5 than the present climate due to increased litterfall and accelerated carbon cycling.
This research presents an improved representation of forest plant functional types (PFT) within the CLM5 model, which can be utilized to simulate carbon stocks and fluxes in Southeast Asia. Furthermore, it provides valuable long-term insights into the impacts of converting forests into oil palm and rubber plantations and the resilience of these land uses to climate change.2025-04-3
Sustainable Agri-Food Systems: Climate Change, Food Prices, and Macroeconomic Dynamics
Get PDFAgri-food systems are integral to achieving at least 12 of the 17 Sustainable Development Goals (SDGs). Nevertheless, agri-food systems are both a victim of and contributor to climate change. A comprehensive understanding of climate-induced welfare losses, the factors shaping low-carbon transitions, and the effects of emissions abatement within agri-food systems is crucial for developing sustainable agri-food systems. In light of this, we first evaluate the impacts of extreme heat on wage losses in the Chinese agri-food industry. We then identify the key factors influencing cooking fuel transitions in rural China using machine learning algorithms. Based on the Dynamic Stochastic General Equilibrium (DSGE) model, we further investigate the macroeconomic effects of implementing a food carbon tax and abolishing the agricultural diesel subsidy. Finally, we evaluate the impact of food price fluctuations resulting from exogenous shocks on macroeconomic dynamics.
By adopting plausibly exogenous year-to-year temperature variations, the first topic reveals that extreme heat is associated with a decrease in worker wages and that these welfare losses can be attributed to the adverse impacts of extremely hot days on worker productivity. We also observe that, compared to male workers, female workers are more likely to bear wage losses when exposed to extremely hot weather. Furthermore, workers in private firms may experience more wage losses due to extremely hot days than those in other ownership types. In the long term, wage losses induced by climate change are projected to rise by 10.93% under RCP8.5, if no extra adaptation actions are implemented.
The second topic leverages machine learning algorithms to predict cooking fuel transitions in rural China. Our analysis reveals that the random forest algorithm achieves superior prediction accuracy compared to alternative models. Overall, we find that environmental and geospatial predictors, obtained from remote sensing data, demonstrate considerable potential in predicting cooking fuel transitions, in contrast to traditional socioeconomic predictors. Notably, we identify rural income and nighttime light intensity as the two most critical factors affecting these transitions. Furthermore, under a positive shock of 75% to both average rural income and nighttime light intensity, the usage rate of non-solid cooking fuels increases by around 70% and 29%, respectively, with this effect being particularly pronounced in China’s developing regions.
The third topic investigates the effects of a food carbon tax on macroeconomic dynamics in China by employing a quantitative DSGE model with nominal price rigidities. Our simulation results indicate that a food carbon tax shock would trigger a recession and inflation, accompanied by a decline in aggregate consumption and employment. Food security could deteriorate due to the rising food consumption costs and declining agricultural growth induced by the food carbon tax shock. Furthermore, flexible food prices and increasing consumption substitution elasticity would amplify the macroeconomic effects of the food carbon tax. A careful trade-off between carbon tax and macroeconomic stability, a transition in food consumption structure, and adjustments in monetary policy could mitigate the adverse effects of the shock.
The fourth topic develops a heterogeneous DSGE model incorporating both agricultural and non-agricultural sectors to simulate the potential macroeconomic effects of abolishing the agricultural diesel subsidy in Germany. Our impulse results reveal that the extensive and intensive margins of diesel demand would decrease by 8.0% and 7.2%, respectively, following the abolition of diesel subsidies. Furthermore, the costs of diesel inputs would increase by approximately 4.6%, accompanied by a 0.76% decline in agricultural outputs. Despite the modest macroeconomic responses (e.g., GDP, aggregate consumption, and inflation) to the policy, its impact could be amplified in the context of the Russia-Ukraine conflict.
The final topic evaluates the impact of food price fluctuations caused by exogenous shocks on macroeconomic dynamics in the United States. Calibration and Bayesian estimation methods are employed to acquire the parameters involved in this model. Our findings indicate that a 10% surge in food prices would magnify the adverse macroeconomic effects compared to a 2% increase in food prices. Importantly, a quarter of headline inflation in the “5C” era can be attributed to food price increases. Furthermore, food price shocks lead to a reduction in real GDP and aggregate consumption. Finally, a higher labor substitution parameter and lower consumption substitution elasticity would amplify the recession in the “5C” era. A moderate monetary policy can mitigate the decline in real GDP and consumption caused by higher food prices, but may exacerbate inflation.
Based on these findings, this dissertation generates several policy implications as follows. First, there is an essential role for the government in preventing workers, especially females, from experiencing welfare losses caused by extreme heat. This study provides evidence for the government to establish high-temperature subsidy standards for workers. Second, we reveal the primary factors driving cooking fuel transitions: rural income and nighttime light intensity. Thus, interventions that aim to increase farmers’ income and initiatives to enhance electricity infrastructure will be effective in facilitating cooking fuel transitions in rural areas. Third, when implementing a food carbon tax, policymakers should carefully balance agricultural emissions abatement, economic stability, and food security. Fourth, our simulation results, indicating that the Russia-Ukraine conflict could amplify farmers’ expenditures on agricultural diesel induced by abolishing agricultural fuel subsidies, hint that policymakers might find it beneficial to consider delaying or implementing the plan in stages as an important policy entry point. Finally, our estimations underline the importance for policymakers to consider the impact of food price shocks on the macroeconomic dynamics, especially in the “5C” era.2025-05-0
Synthesis of Artificial Nucleotides for Biological Applications
Get PDFThis thesis explores the synthesis of nucleotides, the building blocks of DNA and RNA, two essential molecules in living cells. One project focused on developing a more effective ligand for orotidine-5’-monophosphate decarboxylase (OMPDC), a highly efficient enzyme that functions without cofactors. Despite its efficiency, the enzymatic mechanism is not yet fully understood. To gain deeper insights into the human OMPDC-substrate complex, we studied both known and novel analogues of the substrate (OMP) and product (UMP), aiming to design a more effective OMPDC inhibitor. The second project investigated phosphorodiamidate morpholino oligonucleotides (PMOs), promising nucleic acid analogues for gene modulation and therapeutic applications. However, PMOs contain a chiral phosphorus centre, leading to diastereomeric mixtures that may vary in biological activity. To address this challenge, we explored a novel methanediamine-based linker as a non-chiral alternative, revisited the synthesis of the known carbamate linker, and expanded the nucleobase alphabet for the reported glycine linker.2025-05-2
Organic matter preservation in the presence of variable mineralogical matrices – clues to the interpretation of Precambrian biosignatures
Get PDFHydrothermal environments, such as terrestrial hot spring settings, harbored life on the early Earth. However, the scarcity of Precambrian rocks, particularly hydrothermal deposits, hinders the reconstruction of the biological history of these early Earth systems. To overcome this challenge, it is essential to investigate known ancient hydrothermal deposits and combine these investigations with laboratory experiments simulating conditions to which biosignatures are exposed. Therefore, this thesis focuses on (i) the investigation of carbonaceous matter (CM) within hydrothermally deposited black bedded barite from the approximately 3.5 billion-year-old Dresser Formation in Western Australia, and (ii) the incorporation of molecular organic matter within siliceous hot spring deposits through laboratory experiments. To answer whether CM in the hydrothermally deposited black bedded barite from the Dresser Formation is syngenetic to the host rock and of biogenic origin. Furthermore, to investigate if the presence of silica in a hydrothermal environment impacts the preservation potential of organic molecules. Overall, this thesis seeks to provide insights into the preservation potential of biosignatures in hydrothermal environments and discuss the implications for biosignature preservation in Precambrian rocks.
The first study (chapter 2) investigates the presence of CM in ~ 3.5 Ga hydrothermal black bedded barites from the Dresser Formation (Pilbara Craton, Western Australia). Raman spectroscopy mapping revealed three distinct populations of CM: (i) CM at single growth bands of barite crystals (most frequent), (ii) CM within the barite matrix, and (iii) CM in 50–300 µm wide secondary quartz veins that cross-cut the black bedded barite. Calculating maximum metamorphic temperatures based on the Raman spectra showed that CM in secondary quartz veins was introduced after the main metamorphic event, which occurred ~ 3.3 Ga ago. Further analysis using near edge X-ray absorption fine structure (NEXAFS) and solid-state nuclear magnetic resonance (NMR) analysis revealed a high aromatic nature of CM (~ 65 %), together with an aliphatic component (~ 35 %). Stable carbon isotope (δ13C) measurements using secondary ion mass spectrometry (SIMS) showed a wide range of
depleted values (− 33.4 ‰ to − 16.5 ‰), consistent with a biogenic origin of CM. In conclusion the CM within the barite is syngenetic to the host rock and formed at least partly by microorganisms using multiple metabolic pathways. Different pathways for the input of CM into the barite are discussed, including the cycling of biological organic material within the hydrothermal system.
The second study (chapter 3) is a re-evaluation of the Raman spectroscopy data from the first study using an alternative fitting method. This showed that the CM in the secondary quartz veins had been exposed to peak metamorphic temperatures of approximately 260 °C. This confirms that the quartz vein-associated CM is a secondary addition that entered the system after the peak metamorphic event, making it at least 200 million years younger than the barite-hosted CM.
The third study (chapter 4) examines the effect of laboratory heating on archaeal lipids (archaeol and isoprenoid glycerol dialkyl glycerol tetraethers (isoGDGTs)) in the presence and absence of silica. The experiments involved heating single compounds as well as a total lipid extract (TLE) from a microbial mat at 250 °C and 300 bar for 14 days in closed gold capsules. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to examine the mineral phase before and after heating. This showed that heating with single organic compounds led to the formation of small silica microspheres (~ 10 µm), whereas heating with the TLE resulted in irregularly shaped silica grains. Gas chromatography-mass spectrometry (GC–MS) analysis revealed an enhanced decomposition of archaeol in the presence of silica, while isoGDGTs were unaffected by it. However, other organic compounds within the microbial mat TLE seemed to exert a buffering or shielding mechanism on isoGDGTs, increasing their preservation potential. In contrast, archaeol was not affected in the same way. These heating experiments showed that the preservation of archaeal lipids depends on (i) the silica matrix, (ii) their molecular structure, and (iii) the presence of other organic compounds.
The fourth study (chapter 5) examines the molecular-level changes and transformations for selected 13C-depleted isoprenoid hydrocarbons and n-tricosenes within the microbial mat TLE during heating in the presence and absence of silica. GC–MS analysis revealed that heating caused n-tricos-10(Z)-ene to partially transform into n-tricos-10(E)-ene and n-tricosane, while unsaturated pentamethylicosane (PMI∆) was partially hydrogenated to pentamethylicosane (PMI). Additionally, a small portion of acyclic isoprenoids containing functional groups or double bonds (such as phytanol, phytene, PMI∆) were transformed into isoprenoid thiophenes. Furthermore, a tetracyclic isoprenoid hydrocarbon with a highly negative δ13C value was identified in the original hydrocarbon fraction of the TLE. The results show that silica enhanced the degradation of the described compounds with isoprenoid parts, likely due to hydroxyl radicals.
In summary (chapter 6), the individual chapter findings provide insight into the preservation potential of biosignature in hydrothermal environments. Hydrothermal deposits from the Archean can preserve primary biosignatures, but it is essential to consider the possibility of secondary introduction of organic material. However, the presence of a siliceous matrix can enhance the decomposition of certain organic molecular compounds, such as archaeol, PMI, and isoprenoid thiophenes. To gain a comprehensive understanding of biosignature preservation, combining results from ancient and modern samples with laboratory simulations is essential. Such a multidisciplinary approach provides valuable insights into the overall significance and interpretation of biosignatures in Precambrian rocks2025-05-1
Prospective Evaluation of Prognostic Markers of Kidney Injury in Cardiorenal Syndrome: Effect of SGLT2 Inhibitors on Parameters of Renal Congestion
No full textDas kardiorenale Syndrom, das als gemeinsames Auftreten von Nieren- und Herzerkrankungen definiert wird, ist kein seltenes Phänomen im klinischen Alltag. Die renalvenöse Kongestion spielt eine wesentliche Rolle in der Pathophysiologie und Prognose des kardiorenalen Syndroms. Zur Beurteilung und Quantifizierung der renalvenösen Kongestion stellt sich die intrarenale Dopplersonographie als eine nichtinvasive Methode dar. Das intrarenale venöse Flussprofil ist unter physiologischen Bedingungen kontinuierlich und der venöse Impedanz-Index hat einen niedrigen Wert. Die Behandlung des kardiorenalen Syndroms mit Inhibitoren des Natrium/Glucose-Cotransporters 2 (SGLT2-Inhibitoren) ist vielversprechend. Viele randomisierten kontrollierten Studien zeigten einen prognoseverbessernden Effekt dieser Stoffklasse bei Herz- und Niereninsuffizienz. Die Auswirkung einer Therapie mit SGLT2-Inhibitoren auf die dopplersonographischen Parameter der renalvenösen Kongestion ist noch nicht bekannt und ist Gegenstand dieser Arbeit. Die klinisch-prospektive Beobachtungsstudie erfolgte an 64 Patienten mit chronischer Nie-renerkrankung und einem kardiorenalen Risikoprofil (mittlere eGFR 42,9 ml/min/1,73m2; 56% wiesen eine Herzinsuffizienz und 37,5% Diabetes mellitus Typ 2 auf), bei denen im Rahmen der good clinical praxis eine Therapie mit einem SGLT2-Inhibitor (Dapa- oder Empagliflozin) begonnen wurde. Bei diesen Patienten wurde vor Beginn der Therapie eine intrarenale Dopplersonographie durchgeführt. Bei 57 Patienten wurde diese nach sechsmonatiger Einnahme eines SGLT2-Inhibtors wiederholt und es zeigte sich eine Reduktion des mittleren venösen Impedanz-Index der rechten Interlobar- und Hilusvenen um 0,13 (p < 0,01) und die Patientenanzahl, die ein kontinuierliches Flussprofil aufweisen, stieg um über 15% an (p < 0,05). Außerdem beobachtete man eine Erhöhung des Kreatininspiegels im Plasma um 0,11 mg/dl und eine Abnahme der eGFR um 2,8 ml/min/1,73m2 (jeweils p = 0,03). Ferner erhöhte sich die α1-Mikroglobulin-Konzentration im Urin nach sechsmonatiger Einnahme eines SGLT2-Inhibitors um 2,6 mg/l (p = 0,01). Der Blutdruck, die Pulswellengeschwindigkeit und die anderen Parameter der Pulswellenanalyse zeigten keine signifikante Änderung. Die durch die natriuretische und glukosurische Wirkung von SGLT2-Inhibitoren entstandene Hypovolämie bewirkt eine Verschiebung der extrazellulären Flüssigkeit vom interstitiellen Raum in den Intravasalraum und somit wird behauptet, dass eine Therapie mit SGLT2-Inhibitoren die renalvenöse Kongestion vermindert. Die Ergebnisse dieser Studie unterstützen diese Hypothese und stellen einen Ausgangspunkt für weitere Forschung, um den Einfluss von SGLT2-Inhibitoren auf die Hämodynamik beim kardiorenalen Syndrom genauer zu untersuchen. Außerdem stellt sich die Frage, welchen Einfluss eine langfristige Therapie mit SGLT2-Inhibitoren auf die Tubuluszellen und die Biomarker der tubulären Schädigung wie das α1-Mikroglobulin nimmt.The cardiorenal syndrome, defined as the concurrent occurrence of kidney and heart disease, is a common phenomenon in clinical practice. Renal venous congestion plays a significant role in the pathophysiology and prognosis of cardiorenal syndrome. Intrarenal Doppler sonography is a noninvasive method for assessing and quantifying renal venous congestion. Under physiological conditions, the intrarenal venous flow profile is continuous, and the venous impedance index is low. Treatment of cardiorenal syndrome with sodium-glucose transporter 2 inhibitors (SGLT2 inhibitors) is promising. Numerous randomized controlled trials have demonstrated the prognostic benefits of this drug class in heart and kidney failure. However, the impact of SGLT2 inhibitor therapy on Doppler sonographic parameters of renal venous congestion remains unknown and is the subject of this study. This prospective observational study included 64 patients with chronic kidney disease and a cardiorenal risk profile (mean eGFR 42.9 ml/min/1.73m²; 56% had heart failure, and 37.5% had type 2 diabetes mellitus), who had an indication for a SGLT2 inhibitor (dapagliflozin or empagliflozin) as part of good clinical practice. Intrarenal Doppler sonography was performed in these patients prior to the initiation of therapy. Follow-up Doppler sonography was conducted in 57 patients after six months of SGLT2 inhibitor therapy, revealing a reduction in the mean venous impedance index of the right interlobar and hilar veins by 0.13 (p < 0.01), and an increase of over 15% in the number of patients exhibiting a continuous flow profile (p < 0.05). Additionally, a rise in plasma creatinine levels by 0.11 mg/dl and a decrease in eGFR by 2.8 ml/min/1.73m² (both p = 0.03) were observed. Furthermore, α1-microglobulin concentration in urine increased by 2.6 mg/l after six months of SGLT2 inhibitor therapy (p = 0.01). Blood pressure, pulse wave velocity, and other pulse wave analysis parameters showed no significant changes. The hypovolemia induced by the natriuretic and glucosuric effects of SGLT2 inhibitors leads to a shift of extracellular fluid from the interstitial space to the intravascular space, suggesting that SGLT2 inhibitor therapy reduces renal venous congestion. The results of this study support this hypothesis and provide a foundation for further research to investigate the effects of SGLT2 inhibitors on hemodynamics in cardiorenal syndrome. Additionally, the long-term effects of SGLT2 inhibitor therapy on renal tubular cells and biomarkers of tubular injury, such as α1-microglobulin, warrant further exploration.2025-03-2
Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study
No full textFührt eine COVID-19 Impfung zu einem retinalen Gefäßverschlusses? - Eine multizentrische Erhebung an deutschen Augenzentren.
Hintergrund:
Untersucht werde sollte ein möglicher Zusammenhang zwischen dem Auftreten von retinalen Gefäßverschlüssen und einer Impfung gegen SARS-CoV2.
Methoden:
Diese multizentrische Erhebung an deutschen Augenkliniken wurde im Namen der Retinologischen Gesellschaft durchgeführt. Dazu wurde ein online-Formular zur anonymisierten Patientendateneingabe bereitgestellt. Eingeschlossen wurden Patienten mit Zentralvenenverschluss (ZVV), Venenastverschluss (VAV), Zentralarterienverschluss (ZAV), Arterienastverschluss (AAV) oder einer anteriore ischämische Optikusneuropathie (AION). Die Diagnose musste zwischen dem 01.06.2021 und dem 31.07.2021 gestellt worden sein, der Zeitpunkt der ersten Symptome durfte nicht länger als 12 Wochen zurückliegen. Ein Zusammenhang galt als wahrscheinlich, wenn der Verschluss innerhalb von vier Wochen nach der COVID-19 Impfung eintrat. Neben einer reinen Fallanalyse wurde der Datensatz zusätzlich im Rahmen einer Fall-Kontroll-Studie mit Daten der Gutenberg-Gesundheitsstudie (GHS) analysiert, um regionale und zeitliche Häufungen auszugleichen.
Ergebnisse:
36 der 50 ophthalmologischen Zentren haben sich an der Erhebung beteiligt, insgesamt wurden Datensätze von 515 Patienten eingegeben, bei 421 lagen alle studienrelevanten Daten vor. 332 (78,9%) der Patienten waren mindestens einmal geimpft. 306 (76,7%) der Patienten stellten sich innerhalb von zwei Wochen nach Symptombeginn augenärztlich vor, 350 (83%) innerhalb von vier Wochen. In dem Patientenkollektiv erhielten 49 (50%) der ZVV Patienten, 27 (48%) der VAV Patienten, 14 (33%) der ZAV Patienten, 27 (51%) der AAV Patienten und 38 (54%) Patienten mit der Diagnose einer AION bis zu vier Wochen zuvor eine Impfung gegen COVID-19.
Die GHS-Daten ergaben ebenfalls kein erhöhtes Risiko eines retinalen Gefäßverschlusses innerhalb der ersten vier Wochen nach einer COVID-19-Impfung (OR=1.08; 95%-CI: 0.75-1.56, p=0.67).
Es konnte unabhängig von Art des Gefäßverschlusses und Impfstoffes keine Häufung der Diagnosen im Zusammenhang mit einer Impfung gegen COVID-19 festgestellt werden.
Schlussfolgerungen:
Es besteht kein Hinweis auf ein erhöhtes Risiko für einen retinalen Gefäßverschluss im Anschluss an eine COVID-19 Impfung.Background: To investigate whether vaccination against SARS-CoV-2 is associated with
the onset of retinal vascular occlusive disease (RVOD).
Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were
retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series.
Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case–control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted.
Results: Four hundred and twenty-one subjects presenting during the index period
(61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO,
fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred
and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given
were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-
1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our
case–control analysis integrating population-based data from the GHS yielded no evidence of an
increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with
a vaccination within a 4-week window.
Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.2025-05-0
Der Einfluss von medizinischem Kaltplasma auf kutanes Gewebe und Wunden
Get PDFIn the present study, the effects of medical cold plasma on human skin were investigated. On the one hand, the focus was on the impact of medical cold plasma on measurable parameter changes, particularly the microcirculation of intact skin; on the other hand, the influence of medical cold plasma on wound healing was examined. These investigations were conducted in two separate studies.
In the first study, the influence of medical cold plasma on intact skin was investigated. Ten participants were included in the study. The changes in local tissue factors were observed through the combined application of medical cold plasma and the mechanical pressure required for it, compared to the application of mechanical pressure alone without plasma treatment and a control measurement with no external manipulation.
The observed tissue factors were blood flow, blood flow velocity, postcapillary oxygen saturation, relative hemoglobin content, pH level, skin moisture, and temperature. The observation period was 60 minutes after plasma application, with applications lasting 90, 180, and 270 seconds. It was shown that a significant increase in local microcirculation parameters was achieved through the application of medical cold plasma, but not by mechanical pressure alone.
For an application duration of 270 seconds, an increase in relative hemoglobin content by 5.1%, postcapillary oxygen saturation by 9.1%, and blood flow by 105.5% was demonstrated.
In the second study, the influence of medical cold plasma on hard-to-heal wounds and acute wounds with at least one risk factor for the development of wound healing disorders or chronic wounds was investigated in terms of wound size and healing duration. The results were compared to wound healing based on literature data under standard wound care.
The observation period for this study was 2 years. Twenty participants with a total of 27 wounds were included in the study; of these, 8 were acute wounds and 19 were hard-to-heal wounds. The participants were treated with medical cold plasma three times a week for 180 seconds each, over the course of several months.
Wound size measurements were taken after 4 weeks, 12 weeks, and upon complete wound closure. The average age of the wounds was 49 months. The average wound area was 15 cm². After an average observation period of 14.2 weeks, all acute wounds and 68% of the hard-to-heal wounds had healed. 21% of the hard-to-heal wounds had not fully closed by the end of the observation period; however, their wound size had decreased by 80%. 11% of the hard-to-heal wounds were discontinued during therapy.
In summary of both studies, we were able to demonstrate that the application of medical cold plasma not only enhances the local microcirculation of intact skin but also contributes to improving wound healing in both acute and hard-to-heal wounds.2025-05-1
Establishment of mutagenesis methods for pathophysiological analysis of signaling activity in B lymphocytes
No full textDie Signalübertragung des B-Zell-Rezeptors (BZR) spielt eine entscheidende Rolle bei der Aktivierung, Differenzierung und Immunantwort von B-Zellen. Eine Fehlregulation dieses Signalwegs ist mit verschiedenen Immundefekten und B-Zell-Malignomen verbunden. In dieser Studie wurde ein CRISPR/Cas9-basiertes Geneditierungsprotokoll für primäre humane B-Lymphozyten etabliert, um die funktionellen Auswirkungen von Mutationen in zentralen Signalproteinen, insbesondere SLP65 und CIN85, zu untersuchen. Durch die Optimierung der Elektroporationsbedingungen und der Gentransferstrategien wurde eine hocheffiziente Mutagenesemethode entwickelt, die gezielte genetische Modifikationen in primären B-Zellen ermöglicht, ohne deren Überlebensfähigkeit zu beeinträchtigen. Funktionelle Analysen, darunter Kalzium-Mobilisierungsassays und Protein-Interaktionsstudien, zeigten erhebliche Veränderungen in intrazellulären Signalwegen nach der Inaktivierung von SLP65 und CIN85. Diese Ergebnisse liefern wertvolle Erkenntnisse über die molekularen Mechanismen der BZR-Signalübertragung und unterstreichen das Potenzial der Geneditierung zur Erforschung von B-Zell-assoziierten Immunerkrankungen. Darüber hinaus bietet die etablierte Methodik eine Plattform zur Untersuchung genetischer Polymorphismen, die mit B-Zell-Dysfunktionen in Verbindung stehen, und könnte zur Entwicklung gezielter therapeutischer Ansätze beitragen.B cell receptor (BCR) signaling plays a crucial role in B cell activation, differentiation, and immune response. Dysregulation of this pathway is associated with various immunodeficiencies and B cell malignancies. This study focuses on the establishment of a CRISPR/Cas9-based gene editing protocol for primary human B lymphocytes to investigate the functional impact of mutations in key signaling components, specifically SLP65 and CIN85. By optimizing electroporation conditions and delivery strategies, a highly efficient mutagenesis approach was developed that enables targeted genetic modifications in primary B cells without compromising cell viability. Functional analyses, including calcium mobilization assays and protein interaction studies, revealed significant alterations in intracellular signaling cascades following the disruption of SLP65 and CIN85. These findings provide valuable insights into the molecular mechanisms governing BCR signal transduction and highlight the potential for gene-editing technologies to advance our understanding of B cell-related immune disorders. Furthermore, the established methodology offers a platform for studying genetic polymorphisms associated with B cell dysfunctions and developing targeted therapeutic interventions.2025-05-2
Proteomic analysis of small cell lung cancer
No full textDas kleinzellige Lungenkarzinom ist eine aggressive und rasch fortschreitende Tumorerkrankung aus der Gruppe der neuroendokrinen Lungentumore mit einer schlechten Prognose. Ein maßgeblicher Fortschritt in der Behandlung von Patient*innen mit kleinzelligen Lungenkarzinomen konnte in den letzten Jahren nicht erreicht werden. Ziel dieser Studie war es durch die proteomische Analyse von Gewebe kleinzelliger Lungenkarzinome neue potenzielle Therapieziele zu identifizieren, um die Überlebenszeit und die Lebensqualität von Patient*innen zu verbessern. Hierfür wurden in dieser Studie elf formalin-fixierte und in Paraffin eingebettete Gewebeproben kleinzelliger Lungenkarzinome und sechs Proben gesunden Lungengewebes massenspektrometrisch analysiert und auf Proteinebene miteinander verglichen. Zur Aufreinigung der Proben wurde die FASP-Methode in Kombination mit der Verwendung eines Super-SILAC Spike-In-Proteinvergleichsstandards zur Quantifizierung der identifizierten Proteine angewendet. Durch die Messung von zwei Replikaten einer Probe konnten insgesamt 1088 Proteine quantifiziert werden. Insgesamt zeigten sich 311 Proteine signifikant differentiell exprimiert. Unter den signifikant regulierten Proteinen konnten verschiedene Proteine mit einer möglichen Relevanz für die Tumorbiologie gefunden werden. Annexin A1, welches bekannt ist für seine antiinflammatorische Rolle auf molekularbiologischer Ebene, zeigte sich im Gewebe des kleinzelligen Lungenkarzinoms herunterreguliert. ILF3, welchem eine tumorwachstumsfördernde Rolle zugesprochen wird, zeigte sich im Gewebe des kleinzelligen Lungenkarzinoms signifikant hochreguliert. DNA-PK, die für ihre tumorzellproliferationsfördernden Eigenschaften bekannt ist, war im Gewebe des kleinzelligen Lungenkarzinoms im Vergleich zum tumorfreien Lungengewebe ebenfalls verstärkt exprimiert. Auf Grund ihrer beschriebenen Eigenschaften konnten Annexin-1, DNA-PK und ILF3 als potenzielle neue Therapieziele für die Behandlung von Patient*innen mit kleinzelligem Lungenkarzinom identifiziert werden. Ein erweitertes Kollektiv, bestehend aus 79 NET-Fällen, darunter 32 Fälle kleinzelliger Lungenkarzinome, 13 Fälle großzellig neuroendokriner Karzinome, 25 Fälle typischer Karzinoide und neun Fälle atypischer Karzinoide, wurden anschließend auf die Expression der genannten Proteine untersucht. Die Ergebnisse der massenspektrometrischen Untersuchung konnten im Rahmen dieses Kollektivs immunhistochemisch validiert werden.Small cell lung carcinoma belonging to the group of neuroendocrine tumors of the lung is an aggressive and rapidly progressing tumor disease with a poor prognosis. Significant progress in the treatment of patients with small cell lung cancer has not been achieved in recent years. The aim of this study was to identify new potential therapeutic targets through proteomic analysis of small cell lung cancer tissue in order to improve survival and quality of life for patients. In this study we performed a comparative quantitative proteomic mass spectrometric analysis of eleven formalin-fixed and paraffin-embedded small cell lung cancer tissue samples and six samples of healthy lung tissue. Therefore, proteins were isolated using the FASP method in combination with a Super-SILAC spike-in protein quantification standard. By measuring two replicates of one sample, a total of 1088 proteins could be quantified. 311 proteins showed significantly differentially expressions between small cell lung cancer and healthy lung tissue. Among the significantly regulated proteins, several proteins with potential relevance to tumor biology were identified. Annexin A1, known for its anti-inflammatory role at the molecular biological level, was downregulated in small cell lung cancer tissue. ILF3, which is believed to have a tumor growth-promoting role, was significantly upregulated in small cell lung cancer tissue. DNA-PK, known for its tumor cell proliferation-promoting properties, was also found to be upregulated in small cell lung cancer tissue compared to tumor-free lung tissue. Based on their described properties, Annexin-1, DNA-PK, and ILF3 were identified as potential new therapeutic targets for the treatment of patients with small cell lung cancer. An expanded sample collective consisting of 79 NET cases, including 32 cases of small cell lung carcinoma, 13 cases of large cell neuroendocrine carcinoma, 25 cases of typical carcinoids, and nine cases of atypical carcinoids, were subsequently examined for the expression of these proteins. The results of the mass spectrometric analysis were validated immunohistochemically within this sample collective.2025-06-0
Evaluation der nicht-invasiven Leberelastizitäsmessung mittels 2D-Scherwellen-Elastographie (LOGIQ E9 shear wave elastography) im Verlauf der Gewichtsreduktion bei Adipositas im Rahmen des Therapiekonzeptes OPTIFAST®-52
Get PDFDie nicht-alkoholische Fettlebererkrankung (NAFLD) stellt aufgrund ihrer hohen Prävalenz und des potenziell asymptomatischen Verlaufs eine Herausforderung in der Medizin dar. Die NAFLD kann sich chronologisch zu einer nicht-alkoholischen Steatohepatitis, einer Leberfibrose, einer Leberzirrhose und einem hepatozellulärem Karzinom weiterentwickeln. Bis zum Stadium der Leberfibrose ist die NAFLD reversibel. Da die Leberfibrose mit einem erhöhten Mortalitätsrisiko einhergeht, ist ihre präzise Beurteilung von entscheidender Bedeutung. Adipositas und Diabetes Typ 2 sind die wesentlichen Risikofaktoren der NAFLD. Bei adipösen Menschen ist die apparative Diagnostik der NAFLD eine Herausforderung.
In der vorliegenden Studie wurde für die Lebersteifigkeitsmessung das scherwellenbasierte Elastographiegerät Logiq E9 verwendet. Die im Adipositas-Zentrum der Universitätsmedizin Göttingen rekrutierten Studienteilnehmer (n = 67) nahmen am therapeutischen Gewichtsreduktionsprogramm Optifast®-52 teil. Die Datenerhebung fand dreizeitig statt: vor der Fastenphase, nach der Fastenphase, sowie nach der Stabilisierungsphase. Neben der Lebersteifigkeitsmessung wurde außerdem sonographisch der Grad der Steatosis hepatis ermittelt und der NAFLD-Fibrosis-Score (NFS) bestimmt.
Während der Fastenphase verringerte sich der Body-Mass-Index (BMI) von ursprünglich 44,20 ± 9,41 kg/m² auf 36,97 ± 7,83 kg/m². In der anschließenden Stabilisierungsphase war ein weiterer Rückgang des BMI auf 35,00 ± 9,49 kg/m² zu verzeichnen. Parallel dazu nahm der Anteil der Teilnehmer*innen mit einer niedrigen Wahrscheinlichkeit für eine Leberfibrose laut NFS von anfangs 18 % zunächst auf 27 % und schließlich auf 48 % zu. Der Anteil jener mit einer hohen Wahrscheinlichkeit für eine Fibrose sank hingegen von 22 % auf 9 % und später auf 4 %. Zu Beginn des Programms zeigten lediglich 1 % der Teilnehmenden keine sonographischen Hinweise auf eine Leberverfettung. Nach der Fastenphase stieg dieser Anteil auf 52 % und erreichte nach der Stabilisierungsphase 79 %.
Trotz der signifikanten Veränderungen des NFS und der signifikanten Besserung der Steatosis hepatis zeigte sich keine entsprechende Veränderung in den Messwerten der Lebersteifigkeit. Die Messung der Lebersteifigkeit war zu Beginn des Programms bei 55,2 % der Teilnehmenden erfolgreich durchführbar, nach der Fastenphase bei 68,7 % und nach der Stabilisierungsphase bei 80,6 %. Die Erfolgsrate stand dabei in umgekehrtem Zusammenhang mit der Dicke der Bauchwand oberhalb des rechten Leberlappens, des Taillenumfangs und des BMI. Laut den Cut-off-Werten des Herstellers war im Probandenkollektiv weder eine Leberfibrose vorhanden, noch hatte die Gewichtsreduktion einen protektiven Effekt auf die Lebersteifigkeit. Zusammenfassend erscheint der routinemäßige Einsatz des eingesetzten Elastographiegeräts zur Beurteilung einer potenziellen Leberfibrose bei Patient*innen mit morbider Adipositas zum Zeitpunkt der Studie nicht als sinnvoll.Due to its high prevalence and potentially asymptomatic course, non-alcoholic fatty liver disease (NAFLD) remains a challenge in medicine. NAFLD may progress to non-alcoholic steatohepatitis (NASH) and eventually lead to liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Until its progression to fibrosis, NAFLD is a potentially reversible condition. Liver fibrosis poses an increased mortality risk and therefore requires careful assessment. Obesity and type 2 diabetes are the most important risk factors for NAFLD. In obese people, the instrument-based diagnosis of NAFLD is challenging.
In the present study, shear wave elastography (SWE) measurements were performed using a Logiq E9 device to assess liver stiffness. The individuals (n = 67) were recruited at the obesity clinic of the University Medical Center Göttingen where they participated in the Optifast®-52 therapeutic weight reduction program. The data was collected in three stages: before and after the fasting period, as well as after the stabilization period. In addition to measuring liver stiffness, the degree of hepatic steatosis was determined through an abdominal ultrasound examination and the NAFLD fibrosis score (NFS) was calculated.
During the fasting period, the body mass index (BMI) decreased from originally 44.20 ± 9.41 kg/m² to 36.97 ± 7.83 kg/m². In the subsequent stabilization period, there was a further decrease in BMI to 35.00 ± 9.49 kg/m². At the same time, the proportion of participants with a low probability of liver fibrosis according to the NFS increased from initially 18 % to 27 % and finally to 48 %. In contrast, the proportion of participants with a high probability of fibrosis fell from 22 % to 9 % and eventually decreased to 4 %. At the beginning of the program, only 1 % of the participants showed no sonographic evidence of a fatty liver. After the fasting period, this proportion increased to 52 % and, after the stabilization period, reached 79 %.
Despite the significant changes in NFS and the significant improvement in hepatic steatosis, there was no corresponding change in liver stiffness, which was successfully measured in 55.2 % of participants at the start of the program, 68.7 % after the fasting period, and 80.6 % after the stabilization period. The success rate was inversely proportional to the thickness of the abdominal wall above the right lobe of the liver, waist circumference, and BMI. According to the manufacturer's cut-off values, there was no liver fibrosis in the subject group, nor did the weight reduction have a protective effect on liver stiffness. In conclusion, the routine use of the elastography device used to assess potential liver fibrosis in patients with morbid obesity does not appear to be appropriate at the time of the study.2025-05-2