Journals
2025 EN
Pabba Maruthi K. · Kuba Miroslav · Kraus Tomáš
+9 more
Abstract Chromatin dynamics play a crucial role in cellular differentiation, yet tools for studying global chromatin mobility in living cells remain limited. Here, a novel probe is developeded for the metabolic labeling of chromatin and tracking its mobility during neural differentiation. The labeling system utilizes a newly developed silicon rhodamine‐conjugated deoxycytidine triphosphate (dC SiR TP). It is shown that this dCTP is efficiently delivered into living human induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) via a synthetic transporter (SNTT1). Using correlative confocal microscopy and stimulated emission depletion (STED) super‐resolution microscopy, the sizes of labeled chromatin domains are quantified. Time‐lapse super‐resolution microscopy combined with single particle tracking revealed that chromatin mobility decreases during the transition from iPSCs (pluripotent state) to NSCs and neurons (differentiated state). This reduction in mobility correlates with the differentiation state, reflecting changes in chromatin organization during cell fate commitment. Concomitant mechanistic insights obtained from micrococcal nuclease digestion assays, chromatin compaction, and histone modification analyses revealed a decrease in chromatin accessibility during neuronal differentiation. These data indicate that chromatin adopts a more constrained structure with reduced accessibility and increased heterochromatin‐associated histone modifications. These findings provide new insights into chromatin regulation during neurogenesis.
Journals
2025 EN
Trautmann Christine L. · Ghosh Adhideb · Kalkan Ali Kerem
+2 more
3D Tissue‐Engineered Bovine Muscles This cover illustrates efforts to produce cultivated meat from cow muscle cells. In the background, a herd of cows grazes in the Swiss Alps. Muscle samples taken from these cows enabled in vitro production of muscle fibers, which were further enhanced with small molecule treatments to better mimic authentic in vivo muscle tissue. These findings carry potential implications for the improved generation of cultivated meat products. The cover creatively visualizes results by Christine L. Trautmann, Ori Bar‐Nur, and colleagues, who report in article number 2413998 a unique small molecule cocktail that improves bovine muscle cell formation in 2D and 3D systems.
Journals
2025 EN
Ermis Sena · Altinisik Sinem · Catoglu Fahri
+5 more
Abstract Due to the increasing global demand for electrical energy, the fabrication of advanced energy storage devices, such as supercapacitors (SCs), with outstanding performance is of paramount importance. Herein, the facile light‐induced synthesis of a conjugated conductive polymer, namely, poly(guaiazulene) (PGz) is reported on, using a naturally available, low‐cost monomer, guaiazulene (Gz). PGz and PGz_rGO (obtained by combining PGz with reduced graphene oxide (rGO)) exhibited high‐performance supercapacitor (SC) electrode properties, including remarkable specific capacitance (52.75 F g −1 at 0.24 A g −1 and 258.6 F g −1 at 5.00 A g −1 , respectively), excellent cycling stability (97.1% and 94.0% stability after 5000 cycles), high power density (95.5 and 2118.8 W kg −1 ), and, most importantly, high energy density (5.81 and 30.57 Wh kg −1 ). These superior features are attributed to the hierarchical porous nature and high electrical/ionic conductivities of the photochemically obtained PGz. Contrary to previous techniques that require harsh reaction conditions, such as carbonization and coupling reactions, the reported photopolymerization involves solely the irradiation of an ethyl acetate solution of a Gz‐organic photoinitiator (2‐bromoacetophenone) mixture. The photochemical synthesis described here provides a powerful method to produce a sustainable and high‐performance SC electrode material, offering a great alternative to commercial SCs.
Journals
2025 EN
Kralj Suzana · Artuk Kerem · Wieczorek Alexander
+7 more
Abstract Cesium‐formamidinium lead iodide (Cs x FA 1‐x PbI 3 ) perovskites are a promising methylammonium‐free alternative for efficient single‐junction solar cells. However, they have not been fully explored by vapor‐phase deposition techniques. Herein, a template‐assisted approach is demonstrated for the growth of Cs x FA 1‐x PbI 3 perovskite films using pulsed laser deposition (PLD) from a single‐source target of mixed precursors. Implementing a lead iodide (PbI 2 ) + Cs x FA 1‐x PbI 3 tailored template, phase‐pure Cs x FA 1‐x PbI 3 films with uniform coverage on both planar and textured substrates are achieved. Compositional analysis via X‐ray fluorescence confirms near‐stoichiometric transfer of the inorganic cations (Cs/Pb), with identical Cs 0.2 FA 0.8 PbI 3 composition and a bandgap of 1.58 eV achieved in templated and non‐templated films. However, the presence of the template proves essential for attaining phase‐pure films in the photoactive cubic (α‐) phase. Proof‐of‐concept solar cells fabricated with templated‐PLD α‐Cs x FA 1‐x PbI 3 achieve an efficiency exceeding 12.9% on 0.1 cm 2 area devices without the employment of passivation approaches. Additionally, increasing deposition rates does not alter the phase, morphology, or optoelectronic properties of the templated films on textured substrates, indicating the robustness of this methodology. The compositional control of PLD for Cs‐FA‐based perovskites is showcased, and template‐assisted growth is demonstrated as a reliable pathway to high‐quality reproducible perovskite films.
Journals
2025 EN
Arı Ayşe Burcu Doğan · Arı Hasan · Türkyılmaz Ayberk
+4 more
ABSTRACT Nivelon‐Nivelon‐Mabille syndrome (NNMS, #600092) is an extremely rare genetic disorder characterized by microcephaly, central nervous system abnormalities, skeletal anomalies, and 46,XY disorders of sex development. It is caused by biallelic variants in the HHAT gene, which encodes the Hedgehog acyltransferase (HHAT) protein. To date, only eight patients with NNMS have been reported in the literature. In this study, four new patients from two unrelated families were presented, exhibiting distinct phenotypic features including 46,XY gonadal dysgenesis, microcephaly, microphthalmia, ocular coloboma, skeletal dysplasia, and cerebellar vermis hypoplasia. Ptosis and marked visual impairment were present only in the current study. NNMS was considered with the present clinical and radiological findings for four patients, and whole exome analysis revealed three novel variants of the HHAT gene. In silico analyses were performed to provide insights into the structural and functional effects of these genetic variants on the HHAT protein. Accurate diagnosis is crucial for increasing clinical awareness and offering genetic counseling to affected families.
Journals
2025 DE
Schuhmann Fabian · Akkaya Kerem Can · Puchkov Dmytro
+4 more
Abstract Durch Cross‐Linking‐Massenspektrometrie (XL‐MS) wird die Quantifizierung von Protein‐Protein‐Interaktionen auf zellulärer Ebene ermöglicht. Werden alle Teile eines Mitrochondrions analysiert, kann die schiere Anzahl der Verbindungen eine einfache Clusteranalyse unübersichtlich und uninformatif machen. Um diesem Hindernis zu begegnen, verbinden wir die XL‐MS‐Daten, Daten aus der 3D‐Elektronenmikroskopiedaten und Lokalisierungsannotationen mit einer grobkörnige Molekulardynamiksimulation. Auf diese Weise lassen sich alle Daten sortieren und die Cluster besser zugänglich und interpretierbar machen. Im Falle von Mitochondrien identifiziert diese Methode mit Hilfe von insgesamt 6,9 Millisekunden langen Simulationen erfolgreich bekannte und unbekannte Proteincluster und zeigt die Verteilung der inneren mitochondrialen Membranproteine auf, was eine genauere Lokalisierung innerhalb der einzelnen Segmente ermöglicht. Unser integrativer Ansatz legt nahe, dass zwei bisher nicht eindeutig lokalisierte Proteine FAM162A und TMEM126A in der Cristae angesiedelt sind. Dies wird durch hochauflösende Mikroskopie bestätigt. Zusammengenommen, zeigt dies das große Potenzial des vorgestellten Ansatzes.
Journals
2025 EN
Schuhmann Fabian · Akkaya Kerem Can · Puchkov Dmytro
+4 more
Abstract Cross‐linking mass spectrometry (XL‐MS) enables the mapping of protein‐protein interactions on the cellular level. When applied to all compartments of mitochondria, the sheer number of cross‐links and connections can be overwhelming, rendering simple cluster analyses convoluted and uninformative. To address this limitation, we integrate the XL‐MS data, 3D electron microscopy data, and localization annotations with a supra coarse‐grained molecular dynamics simulation to sort all data, making clusters more accessible and interpretable. In the context of mitochondria, this method, through a total of 6.9 milliseconds of simulations, successfully identifies known, suggests unknown protein clusters, and reveals the distribution of inner mitochondrial membrane proteins allowing a more precise localization within compartments. Our integrative approach suggests, that two so‐far ambigiously placed proteins FAM162A and TMEM126A are localized in the cristae, which is validated through super resolution microscopy. Together, this demonstrates the strong potential of the presented approach.
Journals
2025 EN
Badilli Ulya · Cakir Kerem · Yegen Gizem
+2 more
ABSTRACT Skin aging prevention is increasingly important in cosmetics. Topical application of antioxidants protects the skin against reactive oxygen species (ROS) generated as a result of continuous exposure to UV radiation. Herbal oils offer significant anti‐aging potential due to their antioxidant content. Lipid nanoparticles (i.e., SLN and NLC) have been comprehensively evaluated for dermal drug delivery and cosmetic applications since they offer enhanced skin hydration and improved percutaneous penetration. The latest approach for dermal application is the usage of semi‐solid lipid nanoparticle dispersions, which offer unique advantages. Semi‐solid SLN/NLC dispersions have a suitable consistency for dermal application and can be prepared by a one‐step production method without additional excipients. Furthermore, they preserve the colloidal particle size in spite of their semi‐solid consistency. Development of novel cosmeceutical semi‐solid NLC dispersions containing valuable herbal oils such as pomegranate seed, argan, grape seed, and coconut oils was aimed at in this study. Formulation optimization was performed using a modeling program based on response surface methodology (RSM). Optimum semi‐solid NLC formulation (Opt‐NLC) was prepared using Compritol 888ATO and argan oil at amounts of 0.8403 and 0.5457 g, respectively. The particle size of the Opt‐NLC formulation was found to be 188.6 ± 3.58 nm, which falls within the targeted size range. PDI was also reduced and a more uniform particle size was obtained by optimization. Rheological and mechanical characterization results revealed that Opt‐NLC has suitable properties in terms of product performance and consumer compliance. As a result, formulation optimization of semi‐solid NLC dispersions containing antioxidant herbal oils was successfully performed using RSM methodology.
Journals
2025 EN
Mevorach Yaly · Galili Ori · Bigal Eyal
+14 more
ABSTRACT The dynamics of cetacean populations profoundly shape the survival and well‐being of their members, particularly in nutrient‐deficient and anthropogenically impacted regions like the eastern Mediterranean Sea. The common bottlenose dolphin ( Tursiops truncatus ), one of the most extensively studied cetaceans, exhibits complex and diverse social behaviours worldwide. In Israel, common bottlenose dolphins have been observed and studied since 1993, yet no comprehensive analysis has been made of the derived data to unravel their abundance and social structure. Using photographic sightings collected between 2005 and 2020, this study employs mark‐recapture models and social network analysis to uncover the population's dynamics. Observations along the entire Israeli coastline revealed an average group size of 5.9 dolphins, 3.8 of which had clearly marked dorsal fins. Abundance estimates indicated a stable population of 68–88 individuals present at any time, forming part of a larger superpopulation of approximately 343 dolphins. Within this, 42 mature individuals presented higher site fidelity to the study area and exhibited a fluid fission‐fusion social structure characterized by frequent group changes and short‐term associations. Most identified individuals were observed foraging around fishing trawlers, forming significantly smaller groups and exhibiting lower association indices than those observed in the absence of trawlers. These findings emphasize the existence of a small, partially resident population in the easternmost Mediterranean Sea, highlighting the urgent need for coordinated, region‐wide conservation efforts to protect this vulnerable population, mitigate the impact of fishing trawlers and preserve their dynamic habitat.
Journals
2025 EN
Giryes Sami · Wong Chi · Bridgewood Charlie
+12 more
Objective JAK inhibition (JAKi) is effective in seronegative spondyloarthropathy (SpA) spectrum disorders, but Tyk2 inhibition failed in SpA spectrum ulcerative colitis, and tofacitinib showed minimal benefit in Crohn disease, which highlights the complex role for JAK/STAT signaling in different inflammatory processes. In this study, we investigated whether JAKi might paradoxically activate entheseal innate immunity and aimed to identify the key regulatory cytokines involved in this process. Methods Spinal entheseal tissue was activated with Toll‐like receptor (TLR) agonists, including TLR4 and interleukin‐1 (IL‐1) family proteins, and entheseal T cells were activated with anti‐CD3/anti‐CD28 with IL‐23/IL‐1β. JAKi via upadacitinib (JAK1/JAK2), deucravacitinib (Tyk2), and ritlecitinib (JAK3) inhibition was evaluated using multiplex cytokine assays, intracellular flow, and bulk RNA sequencing (RNAseq) and cytokine blocking or stimulation. Results Following interferon γ stimulation, JAK1 inhibition blocked STAT1 phosphorylation in entheseal cells and strongly blocked activated entheseal T cell tumor necrosis factor α (TNFα), IL‐17A, and IL‐17F production. The opposite effect was evident in entheseal myeloid cell with exaggerated TLR4 and other adjuvant‐mediated cytokine production including IL‐23 (~10‐fold increase; P < 0.001) or TNFα (~10‐fold increase; P < 0.0001). This myeloid effect was induced by upadacitinib and deucravacitinib but not ritlecitinib, suggesting IL‐10R JAK1/Tyk2 signaling. Bulk RNAseq showed a multifaceted impact of JAKi on myeloid activation with strong M1 type monocyte polarization under TLR4 stimulation and JAK1 inhibition confirmed by flow cytometry. Direct IL‐10 inhibition recapitulated inflammatory cytokine elevations and IL‐10R agonist largely, but not completely, rescued this phenotype. Conclusion These findings help explain the emergent efficacy of Tyk2 blockade in SpA spectrum–related arthritis that is not IL‐10 dependent but indicates why such strategies may not be a panacea for SpA spectrum disorder–related intestinal inflammation.