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Probing a Hydrogen-π Interaction Involving a Trapped Water Molecule in the Solid State
No full textThe detection and characterization of trapped
water molecules in chemical entities and biomacromolecules
remains a challenging task for solid materials. We
herein present proton-detected solid-state Nuclear Magnetic
Resonance (NMR) experiments at 100 kHz magicangle
spinning and at high static magnetic-field strengths
(28.2 T) enabling the detection of a single water
molecule fixed in the calix[4]arene cavity of a lanthanide
complex by a combination of three types of noncovalent
interactions. The water proton resonances are
detected at a chemical-shift value close to zero ppm,
which we further confirm by quantum-chemical calculations.
Density Functional Theory calculations pinpoint
to the sensitivity of the proton chemical-shift value for
hydrogen-π interactions. Our study highlights how
proton-detected solid-state NMR is turning into the
method-of-choice in probing weak non-covalent interactions
driving a whole branch of molecular-recognition
events in chemistry and biology
Carborane Analogues of Fenoprofen Exhibit Improved Antitumor Activity
No full textFenoprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX-1 the 'house-keeping' enzyme and COX-2 the induced isoform from pathological stimuli. Unselective inhibition of both COX isoforms results in many side effects, but off-target effects have also been reported. The steric modifications of the drugs could afford the desired COX-2 selectivity. Furthermore, NSAIDs have shown promising cytotoxic properties. The structural modification of fenoprofen using bulky dicarba-closo-dodecaborane(12) (carborane) clusters and the biological evaluation of the carborane analogues for COX inhibition and antitumor potential showed that the carborane analogues exhibit stronger antitumor potential compared to their respective aryl-based compounds
A global synthesis of trends in human experience of nature
No full textThe popular perception that humans are undergoing a global extinction of “experience of nature” (EoN) is poorly supported by
empirical evidence. Here, we provide –to
the best of our knowledge –the
first global systematic review of trends in EoN, identifying
only 18 studies that measured temporal trends in EoN. Of those 18 studies, several reported negative trends over time for both
direct EoN (for example, in-person
visits to parklands) and vicarious EoN (specifically, the presence of nature in cultural products,
such as movies or books), and all were biased toward North America, Western Europe, and Japan. As an initial proxy for
understudied regions, we calculated past trends in three metrics of global EoN opportunities and show that, over the past decades,
the locations where humans live have shifted away from the natural world and become more urban, while forest cover in cities has
decreased. Overall, our results suggest that while EoN may be declining globally, existing evidence is insufficient to assess the magnitude and generality of this phenomenon
Überwindung von Rissen. Digitales Studium der Theologie als verbindender und heilender Faktor
No full textInzidenz und Prädiktoren von Thermoläsionen des Ösophagus und Nervus Vagus bei der High-Power-Short-Duration Ablation von Vorhofflimmern
No full textAims
High-power-short-duration (HPSD) ablation is an effective treatment for atrial fibrillation but poses risks of thermal injuries to the oesophagus and vagus nerve. This study aims to investigate incidence and predictors of thermal injuries, employing machine learning.
Methods and results
A prospective observational study was conducted at Leipzig Heart Centre, Germany, excluding patients with multiple prior ablations. All patients received Ablation Index guided HPSD ablation and subsequent oesophagogastroduodenoscopy. A machine learning algorithm categorized ablation points by atrial location and analysed ablation data, including Ablation Index, focusing on the posterior wall. The study is registered in clinicaltrials.gov (NCT05709756). Between February 2021 and August 2023, 238 patients were enrolled, of whom 18 (7.6%; nine oesophagus, eight vagus nerve, one both) developed thermal injuries, including eight oesophageal erythemata, two ulcers, and no fistula. Higher mean force (15.8 ± 3.9 g vs. 13.6 ± 3.9 g, P = 0.022), ablation point quantity (61.50 ± 20.45 vs. 48.16 ± 19.60, P = 0.007), and total and maximum Ablation Index (24 114 ± 8765 vs. 18 894 ± 7863, P = 0.008; 499 ± 95 vs. 473 ± 44, P = 0.04, respectively) at the posterior wall, but not oesophagus location, correlated significantly with thermal injury occurrence. Patients with thermal injuries had significantly lower distances between left atrium and oesophagus (3.0 ± 1.5 mm vs. 4.4 ± 2.1 mm, P = 0.012) and smaller atrial surface areas (24.9 ± 6.5 cm2 vs. 29.5 ± 7.5 cm2, P = 0.032).
Conclusion
The low thermal lesion’s rate (7.6%) during Ablation Index-guided HPSD ablation for atrial fibrillation is noteworthy. Machine learning based ablation data analysis identified several potential predictors of thermal injuries. The correlation between machine learning output and injury development suggests the potential for a clinical tool to enhance procedural safety.:Abkürzungsverzeichnis
Abbildungsverzeichnis
Einführung
Vorhofflimmern
Pulmonalvenenisolation
Thermoläsionen des Ösophagus und Nervus vagus
Machine Learning
Hypothesen und Methoden
Ablationsstrategie der Studie
Machine Learning-basierte Auswertung der Ablationsdaten
Fragestellung und Zielsetzung
Publikationserklärung
Publikationsmanuskript
Supplementary Material
Zusammenfassung der Arbeit
Literaturverzeichnis
Erklärung über den wissenschaftlichen Beitrag des Promovenden zur Publikation
Erklärung über die eigenständige Abfassung der Arbeit
Lebenslauf
Danksagun
Optical Manipulation of Gb3 Enriched Lipid Domains: Impact of Isomerization on Gb3-Shiga Toxin B Interaction
No full textThe plasma membrane is a complex assembly of
proteins and lipids that can self-assemble in submicroscopic
domains commonly termed “lipid rafts”, which are implicated
in membrane signaling and trafficking. Recently, photosensitive
lipids were introduced to study membrane domain
organization, and photo-isomerization was shown to trigger
the mixing and de-mixing of liquid-ordered (lo) domains in
artificial phase-separated membranes. Here, we synthesized
globotriaosylceramide (Gb3) glycosphingolipids that harbor
an azobenzene moiety at different positions of the fatty acid
to investigate light-induced membrane domain reorganization,
and that serve as specific receptors for the protein Shiga
toxin (STx). Using phase-separated supported lipid bilayers on
mica surfaces doped with four different photo-Gb3 molecules,
we found by fluorescence microscopy and atomic force
microscopy that liquid disordered (ld) domains were formed
within lo domains upon trans-cis photo-isomerization. The
fraction and size of these ld domains were largest for Gb3
molecules with the azobenzene group at the end of the fatty
acid. We further investigated the impact of domain reorganization
on the interaction of the B-subunits of STx with the
photo-Gb3. Fluorescence and atomic force micrographs
clearly demonstrated that STxB binds to the lo phase if Gb3 is
in the trans-configuration, whereas two STxB populations are
formed if the photo-Gb3 is switched to the cis-configuration
highlighting the idea of manipulating lipid-protein interactions
with a light stimulus
Equine skeletal scintigraphy: Comparing normal bone-to-soft tissue ratio 2 and 4 hours after injection with either hydroxymethylene diphosphonate or methylene diphosphonate
No full textBackground: In equine skeletal scintigraphy, there is no information about
the possible influence of different phosphonate compounds on image quality.
Methods: This prospective randomised study determined bone uptake
changes and image quality for hydroxymethylene diphosphonate (HDP) and
methylene diphosphonate (MDP) in equine patients at different time points.
Scintigraphic images of the radius and the tibia of 20 horseswere acquired at 2
and 4 hours after injection of either technetium-labelled HDP or MDP. Three
regions of interest were identified—in the bone diaphysis, adjacent soft tissue
and background area—to determine the normal bone-to-soft tissue ratio
(BSR). Qualitative analysis was performed using a modified scoring system.
Results: In terms of BSR and count rates, HDP showed a slightly better incorporation
into bone compared to MDP, but significant differences were only
detected for count rates at 4 hours after injection (p 0.048). The radiopharmaceutical
used did not influence qualitative image scoring, which was
correlated with the BSR (ρ 0.49; p ≤ 0.001).
Conclusion: The choice of HDP or MDP for equine skeletal scintigraphy does
not seem to substantially affect BSR and qualitative image scoring. Further
studies with a larger sample size, including the evaluation of lesion detection
ability for both bone-seeking agents, are needed
Eating Disorder Examination-Questionnaire für Kinder: Kurzform ChEDE-Q8 und Elternversion ChEDE-QP
No full textEine Einführung in zwei Versionen des Eating Disorder Examination-Questionnaire für Kinder (ChEDE-Q) – die Kurzform ChEDE-Q8 und die Elternversion ChEDE-QP –, die zur Erfassung von Essstörungssymptomen und/oder -psychopathologie bei Kindern und Jugendlichen im Alter von 8 bis 14 Jahren entwickelt wurden, einschließlich der jeweiligen Fragebögen
Is microglial dystrophy a form of cellular senescence?: An analysis of senescence markers in the aged human brain
No full textAging can cause morphological transformation in human microglia indicative of cell
senescence, termed microglial dystrophy. However, cellular senescence is characterized
by additional changes, such as an irregular cell cycle arrest, and a variety of metabolic
and molecular changes including a senescence-associated secretory phenotype, dysfunction
of degradation mechanisms, and altered DNA damage response. Here, we
tested whether dystrophic microglia display customary markers of cell senescence by
performing double and triple staining in sections of the temporal lobe and brain stem
from 14 humans. We found that markers related to oxidative damage, such as upregulation
of 8-hydroxy-20-deoxyguanosine (8-OHdG), hemeoxygenase-1 (HO-1), and y-
H2AX, as well as inclusion of lipofuscin, do not or only exceptionally colocalize with
dystrophic microglia. Further, we did not observe a decline in lamin B1 around nuclear
laminae in either dystrophic or ramified microglia within the same microscopic field.
Only ferritin expression, which is known to increase with aging in CNS microglia, was
frequently observed in dystrophic, but rarely in ramified microglial cells. We conclude
that neither dystrophic nor ramified microglia in human brain exhibit significant expression
of conventional senescence markers associated with oxidative stress, and that ferritin
is the dominant immunophenotypic change related to microglial aging.We suggest
that multiple pathogenic mechanisms other than those driving cellular senescence contribute
to dystrophic transformation of microglia
Projecting Stratocumulus Transitions on the Albedo: Cloud Fraction Relationship Reveals Linearity of Albedo to Droplet Concentrations
No full textSatellite images show solid marine stratocumulus cloud decks (Sc) that break up over the remote
oceans. The Sc breakup is initiated by precipitation and is accompanied by a strong reduction in the cloud
radiative effect. Aerosol has been shown to delay the Sc breakup by postponing the onset of precipitation,
however its climatic effect is uncertain. Here we introduce a new approach that allows us to re-cast currently
observed cloud cover and albedo to their counterfactual cleaner world, enabling the first estimate of the
radiative effect due to delayed cloud breakup. Using simple radiative approximation, the radiative forcing
with respect to pre-industrial times due to delayed Sc breakup is −0.39 W m −2
. The radiative effect changes
nearly linearly with aerosol due to the droplet concentration control on the cloud cover, suggesting a potentially
accelerated warming if the current trend of reduction in aerosol emissions continues.
Plain Language Summary
The response of cloud cover to aerosol is a climatologically important
quantity that has been extremely difficult to estimate. The challenge is that one would need to estimate the
fractional area that is currently overcast, but which would have been partly overcast in a cleaner atmosphere.
Global climate models (GCMs) are one tool to address such a problem. They allow one to change aerosol
levels and to evaluate the cloud response. However, representation of warm, low-level cloud processes,
and in particular aerosol-cloud interactions in GCMs, is inadequate. Here we introduce an observational
method that allows us to re-cast the currently observed cloud cover and albedo of oceanic warm clouds
to their counterfactual state in a cleaner world. We find a linear relationship between the cloud radiative
effect and droplet concentration. If we continue to experience a decrease in aerosol emissions then we
anticipate a reduction in the aerosol-cloud radiative effect. The global annual radiative forcing associated
with anthropogenic aerosol delaying closed cell breakup is found to be −0.39 W