10509 research outputs found
Sort by
MePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing
No full textInternal modifications of mRNA have emerged as widespread and versatile regulatory mechanism to control gene expression at the post-transcriptional level. Most of these modifications are methyl groups, making S-adenosyl-L-methionine (SAM) a central metabolic hub. Here we show that metabolic labeling with a clickable metabolic precursor of SAM, propargyl-selenohomocysteine (PSH), enables detection and identification of various methylation sites. Propargylated A, C, and G nucleosides form at detectable amounts via intracellular generation of the corresponding SAM analogue. Integration into next generation sequencing enables mapping of N6-methyladenosine (m6A) and 5-methylcytidine (m5C) sites in mRNA with single nucleotide precision (MePMe-seq). Analysis of the termination profiles can be used to distinguish m6A from 2′-O-methyladenosine (Am) and N1-methyladenosine (m1A) sites. MePMe-seq overcomes the problems of antibodies for enrichment and sequence-motifs for evaluation, which was limiting previous methodologies. Metabolic labeling via clickable SAM facilitates the joint evaluation of methylation sites in RNA and potentially DNA and proteins
Transcriptomic analysis of Chinese yam (Dioscorea polystachya Turcz.) variants indicates brassinosteroid involvement in tuber development
No full text'Dioscorea' is an important but underutilized genus of flowering plants that grows predominantly in tropical and subtropical regions. Several species, known as yam, develop large underground tubers and aerial bulbils that are used as food. The Chinese yam ('D. polystachya' Turcz.) is one of the few 'Dioscorea' species that grows well in temperate regions and has been proposed as a climate-resilient crop to enhance food security in Europe. However, the fragile, club-like tubers are unsuitable for mechanical harvesting, which is facilitated by shorter and thicker storage organs. Brassinosteroids (BRs) play a key role in plant cell division, cell elongation and proliferation, as well as in the gravitropic response. We collected RNA-Seq data from the head, middle and tip of two tuber shape variants: F60 (long, thin) and F2000 (short, thick). Comparative transcriptome analysis of F60 vs. F2000 revealed 30,229 differentially expressed genes (DEGs), 1,393 of which were differentially expressed in the growing tip. Several DEGs are involved in steroid/BR biosynthesis or signaling, or may be regulated by BRs. The quantification of endogenous BRs revealed higher levels of castasterone (CS), 28-norCS, 28-homoCS and brassinolide in F2000 compared to F60 tubers. The highest BR levels were detected in the growing tip, and CS was the most abundant (439.6 ± 196.41 pmol/g in F2000 and 365.6 ± 112.78 pmol/g in F60). Exogenous 24-epi-brassinolide (epi-BL) treatment (20 nM) in an aeroponic system significantly increased the width-to-length ratio (0.045 ± 0.002) compared to the mock-treated plants (0.03 ± 0.002) after 7 weeks, indicating that exogenous epi-BL produces shorter and thicker tubers. In this study we demonstrate the role of BRs in 'D. polystachya' tuber shape, providing insight into the role of plant hormones in yam storage organ development. We found that BRs can influence tuber shape in Chinese yam by regulating the expression of genes involved cell expansion. Our data can help to improve the efficiency of Chinese yam cultivation, which could provide an alternative food source and thus contribute to future food security in Europe
Type 1 Interferon-Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?
No full textObjective: Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed the required number of ISGs to be included in a composite type 1 IFN score. Methods: Whole blood-derived RNA and clinical data were collected from 171 mostly pediatric patients with connective tissue diseases (CTDs), systemic autoinflammatory diseases (SAIDs), monogenic interferonopathies (IFNPs) and other inflammatory diseases, and from 38 controls. The expression of six previously established ISGs, IL18, and CXCL9 was assessed by real-time polymerase chain reaction (471 samples). Individual and composite gene expression was assessed, and correlation and threshold analyses were performed.
Results: Correlation between ISG expression and clinical disease activity was strongest in CTD, especially in juvenile dermatomyositis (JDM) and IFNP, and modest in patients with SAID. Threshold ISG expression levels for the detection of at least mild clinical disease activity were substantially higher in patients with systemic lupus erythematosus compared with JDM. The correlation of expression levels of limited sets of ISGs and even individual ISGs with clinical disease activity were not inferior to a composite score of six ISGs. Conclusion: In a real-world cohort, individual ISG expression levels robustly reflected clinical disease activity in CTD and IFNP, especially in JDM, which would simplify such analyses in clinical routine and be more cost-effective. Threshold levels varied across diseases, potentially reflecting different mechanisms of type 1 IFN overactivation
Redefining the Fight Against SCLC: Standards, Innovations, and New Horizons
No full textBackground: Small cell lung cancer (SCLC) remains a highly aggressive malignancy with a poor prognosis. Despite multimodal standard therapies, most patients relapse within months, and second-line treatment options such as topotecan offer only limited benefit. Novel therapeutic strategies are therefore urgently needed. Methods: This narrative review is based on a selective literature search conducted via PubMed and ClinicalTrials.gov (last updated June 2025). Results: Emerging treatment strategies include bispecific T-cell engagers (e.g., tarlatamab), antibody-drug conjugates (ADCs) such as sacituzumab govitecan, DS-7300, and ZL-1310, as well as targeted therapies. Among these, tarlatamab has demonstrated improved survival outcomes with an acceptable safety profile and is poised to become the new second-line standard. In contrast, ADCs and targeted agents have shown only modest efficacy and have yet to deliver meaningful survival benefits, often accompanied by increased toxicity. Additionally, the identification of molecular subtypes of SCLC has revealed subtype-specific differences in treatment response. However, clinical translation is challenged by intratumoral heterogeneity, plasticity, and the lack of standardized diagnostic assays. Conclusions: While tarlatamab represents a major therapeutic advancement, other agents remain in early clinical development and require validation in large, randomized trials. The clinical implementation of molecular subtyping remains limited, though it holds promise for future personalized treatment approaches. Despite recent progress, SCLC continues to pose substantial therapeutic challenges, emphasizing the need for improved treatment strategies and validated predictive biomarkers
Regular inclusions of simple unital C*-algebras
No full textWe prove that an inclusion B ⊂ A of simple unital C*-algebras with a finiteindex conditional expectation is regular if and only if there exists a finite group G that admits a cocycle action (α, σ) on the intermediate C*-subalgebra C generated by B and its centralizer CA(B) such that B is outerly α-invariant and (B ⊂ A) ∼= (B ⊂ C ⋊r (α,σ) G). Prior to this characterization, we prove the existence of two-sided and unitary quasi-bases for the minimal conditional expectation of any such inclusion, and also show that such an inclusion has integer Watatani index and depth at most 2
Schlüssel zum Erfolg: Kognitive und metakognitive Prozesse beim Verstehen von Mathematik
No full textDer vorliegende Band widmet sich der Komplexität des Verstehens von Mathematik. Die Beiträge verdeutlichen die zentrale Bedeutung von kognitiven und metakognitiven Prozessen, die für den Erfolg im Mathematikunterricht wesentlich sind. Kognition umfasst die mit Erwerb, Organisation und Gebrauch von Wissen verbundene individuelle geistige Aktivität, Metakognition steht für das Kennen, Steuern und Empfinden der eigenen kognitiven Prozesse.
Zur Sprache kommen kognitionswissenschaftliche Analysen des Lernens, Denkens und Verstehens. Im Fokus stehen dabei spezifische kognitive und metakognitive Aktivitäten. Insbesondere wird erläutert, wie Lernende ihre eigenen Denkvorgänge und ihre Lernstrategien planen, überwachen und anpassen. Dies ist essenziell, um mathematische Aufgaben und Probleme effektiv zu lösen und um das Verstehen von Mathematik nachhaltig zu vertiefen.
Selbstverständlich setzt sich das Buch auch mit der diesbezüglichen Professionalisierung von angehenden Lehrkräften auseinander.
Durchweg bieten die Beiträge unterrichtspraktische Hinweise für Lehrkräfte. Es werden unterrichtliche Vorgehensweisen dargelegt, die die Entwicklung kognitiver und metakognitiver Fähigkeiten der Lernenden fördern. Einen besonderen Stellenwert hat dazu die Nutzung von Reflexionsphasen, um Lernprozesse bewusst zu machen.
Mathematik ist in Ungarn traditionell von hoher kultureller und wissenschaftlicher Bedeutung. Auch an diesem Band der Buchreihe "Mathematiklehren und -lernen in Ungarn" haben sich Autorinnen und Autoren aus verschiedenen Ländern beteiligt, um die beispielgebende Rolle des Landes und den inspirativen Austausch über Grenzen hinweg zum Ausdruck zu bringen
Social Media ist "Riesenglück" für den Buchmarkt:Buchwissenschaftlerin Corinna Norrick-Rühl über die Rolle von Künstlicher Intelligenz und "BookToks" für das gedruckte Wort
No full textVor dem Hintergrund der wachsenden Zahl von mit künstlicher Intelligenz produzierten Büchern auf einigen Plattformen warnt die Buchwissenschaftlerin Prof. Dr. Corinna Norrick-Rühl vor den gesellschaftlichen Gefahren. "Wenn wir irgendwann ausschließlich KI-Texte konsumieren, fehlt es an Menschen, die uns durchdachte Texte liefern", gibt die Expertin in der neuen Folge des "Umdenken"-Podcasts der Universität Münster zu bedenken. Einzelnen" und warnt davor, entsprechende Tools leichtfertig mit Buchinhalten zu "füttern". Gleichwohl habe der technologische Fortschritt auch positive Auswirkungen auf den Buchmarkt. Social-Media-Trends wie "BookTok" auf der Plattform TikTok seien ein "Riesenglück" für die Branche, erklärt die Wissenschaftlerin
Subgeometries of (exceptional) Lie incidence geometries induced by maximal root subsystems
No full textWe consider the following question: when does a Riemannian manifold admit an embedding with a uniformly thick tubular neighborhood in another Riemannian manifold of large dimension
The mitochondrial protein Sod2 is important for the migration, maintenance, and fitness of germ cells
No full textTo maintain a range of cellular functions and to ensure cell survival, cells must control their levels of reactive oxygen species (ROS). The main source of these molecules is the mitochondrial respiration machinery, and the first line of defense against these toxic substances is the mitochondrial enzyme superoxide dismutase 2 (Sod2). Thus, investigating early expression patterns and functions of this protein is critical for understanding how an organism develops ways to protect itself against ROS and enhance tissue fitness. Here, we report on expression pattern and function of zebrafish Sod2, focusing on the role of the protein in migration and maintenance of primordial germ cells during early embryonic development. We provide evidence that Sod2 is involved in purifying selection of vertebrate germ cells, which can contribute to the fitness of the organism in the following generations
The rational HK-conjecture: Transformation groupoids and a revised version
No full textWe prove the rational HK-conjecture for a large class of transformation groupoids in the case when the relevant action has torsion-free stabilizers. A revised version of the rational HK-conjecture in the case of (possibly) torsion stabilizers is introduced and proved for a large class of transformation groupoids. In particular, this revised version holds for Scarparo’s counterexamples to the original rational HK-conjecture. The key tools used are the Baum–Connes conjecture and a Chern character defined by Raven