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Direct observation of triplet–triplet energy transfer in DNA between energy donor and acceptor C-nucleotides
Full text linkInvestigating the migration of excited-state energy in DNA is crucial for a deep understanding of protection mechanisms and light-induced DNA damage. While numerous reports focused on single electron transfer and Förster-type energy transfer in DNA, studies on the Dexter-type triplet–triplet energy transfer are scarce, in particular, those with direct detection of photoexcited triplet states. Herein, we present direct measurements of the distance-dependent triplet–triplet energy transfer rates through DNA by using transient absorption spectroscopy. This was achieved through the synthetic incorporation of thioxanthone as an energy donor and naphthalene as an energy acceptor into a DNA double strand at defined positions. The energy transfer rates strongly depend on the number of A-T base pairs (up to four) separating the energy donor from the energy acceptor. We observed a fast energy transfer rate with a time constant of 17 ns for the DNA sample in which the donor and acceptor are directly adjacent in the DNA. By analyzing two additional donor–acceptor distances, a steep exponential distance dependence with an attenuation factor of 1.15 Å–1 could be obtained. Our results demonstrate that DNA acts as a poor conductor of triplet energy when energy donors with triplet energies below 2.7 eV are used, complementing more indirect studies on sensitized DNA damage
On the genomic basis of mosaic coevolution in a social host-parasite system
Full text link282 Seiten ; Illustrationen, Diagramm
The Impact of evening gaming on cortisol and melatonin levels : findings from a randomized controlled trial
Full text linkVideo games (VGs) are a popular form of entertainment, especially among younger individuals, yet their impact on sleep-related hormonal regulation remains unclear. This randomized controlled trial investigated the effects of evening gaming on cortisol and melatonin—key hormones in the sleep-wake cycle—compared to watching a nature film. Thirty-one male participants (aged 18–37) completed two conditions: 120 minutes of gaming ("League of Legends" or "Counter-Strike: Global Offensive") and 120 minutes of watching a nature film. Salivary samples were collected pre- and post-session and at waking (+15- and +30-minutes post-waking) the next morning.
Cortisol levels showed significant within-condition changes, but no significant differences between conditions were found (t(180.0) = 1.41, p = 0.16). The cortisol awakening response (CAR) increased 15 minutes post-waking and normalized by 30 minutes. Melatonin levels and the Area Under the Curve for Inhibition (AUCI) analysis for both hormones showed no significant differences between gaming and film.
These findings suggest that evening gaming among regular gamers, under controlled conditions, does not disrupt hormonal balance compared to passive film-watching. Habituation to gaming and environmental controls may have mitigated stress responses. Future research should investigate the effects of game novelty, varying player experiences, and diverse populations to develop guidelines for healthy gaming practices.
VG = video games; SCN = Suprachiasmatic Nucleus; HPA = Hypothalamic-Pituitary-Adrenal (Axis); CAR = Cortisol Awaking Response; AUCI = Area Under the Curve for Inhibition; BMI = Body Mass Index; adc = active digital condition pdc = passive digital condition; IGD = Internet Gaming Disorde
Do scoring systems help us to estimate prognosis after mechanical thrombectomy? Data from the German Stroke Registry
Full text linkBackground Numerous scoring systems have been developed to individualize estimation of functional outcome after endovascular thrombectomy (EVT) of acute ischemic stroke. The aim of our study was to assess their utility for clinical practice based on a large cohort from real-world care of EVT.
Methods For 13 082 patients included in the German Stroke Registry Endovascular Treatment (GSR-ET) (July 2015 to December 2021), we calculated the following prognostic tools: pre-interventional PRE-, Totaled Health Risks in Vascular Events – Endovascular therapy (THRIVE-EVT)- and Computed Tomography for Late Endovascular Reperfusion (CLEAR) scores and post-interventional MR PREDICTS@24 hours and BET-score. Area under the receiver operating characteristic curve (AUC) analyses in the total cohort and pre-defined subgroups were performed to determine each tool’s prognostic value for good functional outcome (modified Rankin Scale (mRS) 0–2) and mortality at 90-day follow-up.
Results All pre-interventional tools achieved a moderate prognostic value for predicting good functional outcome (PRE: AUC (95% confidence interval): 0.757 (0.747–0.768), THRIVE-EVT: 0.751 (0.740–0.761), CLEAR: 0.731 (0.72–0.742)), had a higher predictive value than the admission National Institute of Health Stroke Scale ((NIHSS); 0.705 (0.694–0.716), all P0.85), superior to 24-hour NIHSS for all subgroups, except patients <50 years of age.
Conclusion Pre-interventional scoring tools predict functional outcome after EVT better than stroke severity alone. Post-interventionally, the MR PREDICTS@24 hours tool adds predictive value to the 24-hour NIHSS as a single prognostic feature. Multivariate prognostic tools incorporating (post-)procedural information enable individualization of prognosis assessment after EVT under routine-care conditions
Atypical adverse events in a real-world study of long-term immunomodulation for multiple sclerosis and neuromyelitis optica spectrum disorder
Full text linkBackground:
Immunotherapies are integral in managing multiple sclerosis (MS) and related demyelinating diseases, but adverse drug reactions significantly affect the tolerability of disease-modifying therapies (DMTs).
Objectives:
This study aims to assess the safety profile of DMTs within a real-world cohort affected by MS and related diseases and to identify atypical adverse events (AEs) and those of exceptional severity.
Methods:
A retrospective analysis was conducted on 3850 patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and related conditions (2009–2022). Demographic and clinical data were analyzed for patients treated with DMTs. Parameters included prior treatments, AEs, treatment durations, and reasons for discontinuation.
Results:
Of the cohort, 1989 patients (71.1% female) with a median follow-up of 46.3 months during DMT use were included. Monotherapy was employed in 987 patients, while 1002 received sequential DMTs, totaling 3850 treatments. Adverse reactions led to discontinuation in 24.2% of cases, while disease progression accounted for 22.9%. Among 1878 AEs, 31 (1.7%) were atypical, and 59 (3.1%) were unusually severe, which was systematically categorized based on type, timing, and remission.
Conclusion:
Within the confines of this real-world study, DMT administration emerged as generally well tolerated in MS, related demyelinating diseases and NMOSD. The identification of a limited number of atypical AEs, nevertheless, broadens the spectrum of potential complications associated with DMTs. Although weaker evidence for causal associations between drug exposure and observed AEs remains a limitation in observational studies without comparable control groups, this study underscores the value of real-world investigations in offering insights into the long-term safety of DMTs, particularly for rare events
Rezension zu: Tracy, Rosemarie ; Gawlitzek, Ira: Mehrsprachigkeit und Spracherwerb. Tübingen 2023
Full text linkEvaluating genetic regulators of microRNAs using machine learning Mmodels
Full text linkThis study explores the genetic regulators of microRNAs (miRNAs) using a set of machine learning models to predict miRNA expression levels from gene expression data. Employing machine learning, we accurately predicted the expression of 353 human miRNAs (R2 > 0.5), revealing robust miRNA–gene regulatory relationships. By analyzing the coefficients of these predictive models, we identified genetic regulators for each miRNA and highlighted the multifactorial nature of miRNA regulation. Further network analysis uncovered that miRNAs with higher predictive accuracy are more densely connected to their top predictive genes, reflecting strong regulatory control within miRNA–gene networks. To refine these insights, we filtered the miRNA–gene interaction networks to identify miRNAs specifically associated with enriched pathways, such as synaptic function and cardiovascular processes. From this pathway-centric analysis, we present a curated list of miRNAs and their genetic regulators, pinpointing their activity within distinct biological contexts. Additionally, our study provides a comprehensive set of metrics and coefficients for the genes most predictive of miRNA expression, along with a filtered subnetwork of miRNAs linked to specific pathways and phenotypes. By integrating miRNA expression predictors with network analysis and pathway enrichment, this work advances our understanding of miRNA regulatory mechanisms and their roles across distinct biological systems. Our approach enables researchers to train custom models using TCGA data and predict miRNA expression from gene expression inputs
Mantle dynamics in the Mediterranean and plate motion of the Adriatic microplate : insights from 3D thermomechanical modeling
Full text linkThe motion of the Adriatic microplate is thought to be highly sensitive to the surrounding subduction zones and the convergence of Africa and Eurasia. However, our understanding of the mantle dynamics in the Mediterranean region and its effect on plate motion remains incomplete. Here, we present a large set of 3D thermomechanical models of the entire Mediterranean region over the last 35 Myr to understand what controls the motion of the Adriatic microplate. The simulations take the convergence of the African and Arabian plates with the Eurasian plate into account, along with the dynamics of the subduction systems in the western (Apennines-Calabria), central (Dinarides-Hellenides) Mediterranean and in the Alpine-Carpathian region. Our results demonstrate that the subduction systems around Adria are highly coupled, which gives rise to complex asthenospheric flow in the central Mediterranean. We find that the plate motion of the Adriatic microplate over the last 35 Myr is controlled by the interplay of three main factors: (a) the convergence between the African and Eurasian plates, (b) the retreat of the Alpine subduction zone to the north of Adria, and (c) the distance between the Calabrian and Hellenic subduction zones around Adria. Furthermore, in a system characterized by active convergence between Africa and Eurasia, the slab pull exerted by nearby subduction zones can only notably influence the motion of the Adriatic microplate if these subduction zones are located within a few hundred kilometers of Adria
Improving the accuracy in particle concentration measurements of a balloon-borne optical particle counter, UCASS
Full text linkFor balloon-borne detection of aerosols and cloud droplets (diameter 0.4 < Dp < 40 µm), a passive-flow Universal Cloud and Aerosol Sounding System (UCASS) was used, whose sample flow rate is conventionally derived from balloon ascent rates using GPS or pressure measurements. Improvements are achieved by implementing thermal flow sensors (TFSs) 94 mm downstream of the UCASS detection region for continuously measuring true UCASS sample flow velocities. UCASS-mounted TFSs were calibrated during wind tunnel experiments at up to 10 m s−1, and under various angles of attack (AOAs), as these vary during actual balloon ascents. It was found that the TFS calibration is determined with sufficient precision using three calibration points at tunnel flows of ∼ 2, 5, and 8 m s−1, simplifying efficient TFS upgrades of numerous UCASSs. In iso-axial alignment, UCASS flows are accelerated (by ∼ 11.3 %) compared to tunnel flows (at 2–8 m s−1). In-flight comparisons up to 7.5 km in height revealed that UCASS sample flows rarely match the balloon's ascent rate. Laboratory experiments show that equality (vGPS=vTFS) is achieved only at AOA ≠ 0°, potentially affecting the UCASS internal flow pattern and particle transmission efficiency in flight. To minimise errors in calculated UCASS-based particle number concentrations, real-time measurements of the true UCASS flow velocity are recommended
Genderdisparitäten im ärztlichen Rollenverständnis : Untersuchung von Einflussfaktoren auf die Beurteilung der medizinischen Professionalität: eine randomisierte kontrollierte Studie unter Humanmedizinstudierenden : IDEAL-Studie
Full text linkDas vorliegende Forschungsvorhaben untersuchte Einflussfaktoren auf die Wahrnehmung von Arztpersonen, mit besonderem Fokus auf geschlechterspezifische Unterschiede in der Bewertung ärztlicher Professionalität. Basierend auf aktueller Literatur wurde angenommen, dass weibliche Arztpersonen aufgrund bestehender Genderdisparitäten schlechter bewertet werden als männliche. Die explorative, randomisiert kontrollierte IDEAL-Studie wurde erstmals in dieser Form in Deutschland durchgeführt. Grundlage bildete eine Onlinebefragung unter Humanmedizinstudierenden der Johannes Gutenberg-Universität Mainz, die ein fiktives Fallbeispiel bewerteten. Die Ergebnisse zeigten keinen signifikanten Unterschied in der Bewertung der ärztlichen Professionalität zwischen weiblichen und männlichen Arztpersonen. Auch bei den sekundären Endpunkten ergaben sich keine statistisch signifikanten Geschlechterunterschiede. Die Generalisierbarkeit der Resultate ist aufgrund der spezifischen Kohorte eingeschränkt. Mögliche Ursachen für das Ausbleiben geschlechtsspezifischer Unterschiede könnten in einer unvoreingenommenen Wertehaltung der angehenden Arztpersonen sowie in der intrinsischen Motivation der Studienteilnehmenden liegen. Trotz der Studienergebnisse bestehen in der medizinischen Realität weiterhin strukturelle Benachteiligungen für weibliche Arztpersonen, bedingt durch geschlechterspezifische Stereotype und Bias. Die Förderung eines diskriminierungsfreien Umfelds sowie die Sensibilisierung für Genderdisparitäten sind daher weiterhin erforderlich. Zukünftige Untersuchungen sollten größere Stichproben sowie realitätsnahe Szenarien einbeziehen, um geschlechterspezifische Wahrnehmungsunterschiede differenzierter analysieren zu können.III, 99 Seiten ; Diagramm