Synaptic neurotransmission is a critical hallmark of brain activity and one of the first processes affected in neural diseases. Monitoring this process, particularly synaptic vesicle recycling, in living cells has been instrumental in revealing the mechanisms responsible for neurotransmitter release. However, currently available reporters suffer from limitations, such as large probe sizes or limited compatibility for human neurons, hampering the quantitative analysis of synaptic pathophysiology. Here, we describe the NbLumSyt1 toolkit, a panel of nanobody-based affinity probes that target the luminal domain of the synaptic vesicle protein Synaptotagmin 1 (Syt1). These new tools enable quantitative, noninvasive imaging and functional interrogation of Syt1 exo-endocytosis and trafficking in human neurons, with unprecedented precision, versatility and cost efficiency, in technologies ranging from fixed- and live-cell super-resolution imaging to electron microscopy and mass spectrometry. Overall, NbLumSyt1 nanobinders provide a valuable platform for studying synaptic physiology and pathophysiology, benefiting fundamental neuroscience and translational efforts to study and develop treatments for brain-related disorders. Graphical Abstract

Progressive Identitätspolitik ist keine bloße Frage der Anerkennung, sondern sie zielt auf die Überwindung sozialer Herrschaftsverhältnisse ab, die in der Gleichzeitigkeit und Verschränkung verschiedener Unterdrückungssysteme wurzeln. Dieser Beitrag kontextualisiert die Genese der Identitätspolitik auf Grundlage von »Druckerzeugnissen« Schwarzer US-amerikanischer Feminist:innen wie Sojourner Truth, Claudia Jones, Frances Beal und dem Combahee River Collective. Dabei wird deutlich, dass identitätspolitische Kämpfe in diesem Verständnis Kämpfe für universalistische Ideale sind.

Local mRNA translation is required for adaptive changes in the synaptic proteome. The mitogen-activated protein kinase (MAPK) interacting protein kinases 1 and 2 (MNK1 and MNK2) have emerged as key regulators of neuronal translation, primarily through phosphorylation of the eukaryotic initiation factor 4E (eIF4E). The therapeutic benefits of targeting the MNKs are being investigated for nervous system conditions that affect translation, including autism and pain. However, it is still unclear if MNK1 and MNK2 regulate distinct aspects of neuronal translation and how the activity of each kinase is associated with the synaptic and behavioral features linked to MNK signaling. To examine the individual neurobiological functions of each kinase, we used knockout mice lacking either MNK1 or MNK2. We found that knockout of MNK1 and MNK2 leads to different social and cognitive behavioral profiles and distinct alterations of the cortical synaptic proteome, transcriptome, and phosphoproteome. Loss of MNK1 was associated with increased ribosomal protein expression, whereas deletion of MNK2 decreased the expression and phosphorylation of synaptic proteins. Together, our findings provide evidence for a high degree of functional specialization of the MNKs in synaptic compartments and suggest that pharmacological inhibition of individual MNKs may provide more specific targets for neurological disorders.

Tide gauges have been critical sources for sea level research, enabling the development of tidal theory and an understanding of local variations that occur across the global oceans. Tides play important roles in a variety of oceanographic and geodetic applications, and characterizing their spatial variability is valuable for applications ranging from fishing to flood risk management. This manuscript presents the coastal characteristics of ocean tides based on 3591 high-frequency tide gauge observations from the recently updated Global Extreme Sea Level Analysis (GESLA) database. These characteristics range from tidal datums such as Mean High Water (MHW) and the Great Diurnal Range to metrics like the Age of the Tide, Form Factors, updated amplitude trend estimates, and new insights into the regional duration of high tides. Our analysis finds that 125 out of 237 long-time series show statistically significant trends in one or more constituents, from -1.47 to +1.80mmyr-1, while the duration of the high-water stand during spring tides is shown to vary from 1 to 14 h, for an inundation depth of 20 cm. It is anticipated that the results presented will be useful not only to tidal experts but also to a wide range of cross-disciplinary researchers and local communities, aiding their understanding of a vital component of the global Earth system.

Class II histone deacetylases (HDAC) orchestrate T cell-dependent immune responses via the epigenetic control of genes and via the post-translational modification of cytoplasmic and nuclear proteins. However, the contribution of single HDAC family members to the differentiation and function of peripheral CD8 + T cells remains elusive. We here demonstrate that HDAC7-deficiency leads to the upregulation of immune checkpoint molecules, increased apoptosis and disturbed glutamine homeostasis of peripheral murine CD8 + T cells, which we could link to a MEF2D-dependent induction of FasL expression ultimately deterring the survival of HDAC7-deficient CD8 + T cells. Likewise, we observed in mouse models of lymphoma, that mice with a T cell-specific deletion of Hdac7 harbor impaired anti-tumor immune responses in syngeneic transfer models of lymphoma and we found that HDAC7 is required for CD8 + T cell-dependent memory recall responses in models of lymphocytic choriomeningitis virus infection. Taken together, we identify HDAC7 as a central regulator of cellular exhaustion and apoptosis of peripheral CD8 + T cells, controlling CD8 + T cell dependent anti-tumor and anti-viral immunity in mice.

Critical Digital Literacy (CDL) extends basic digital competence to the ability to critically evaluate and engage with digital media's social and ethical dimensions. This scoping review targeted CDL theory and interventions in early childhood, applying PRISMA-ScR and JBI methods; database searches produced twenty-five studies, analyzed descriptively and using thematic analysis approach. The literature displays varied definitions, few age-specific interventions, and a concentration in educational research from the Global North. Core early CDL capacities identified are sociocultural contextualization, reflective perspective-taking, and constructing/deconstructing multimodal narratives. Educational approaches to building CDL included playful and creative multimodal learning, reflective practices, fostering the understanding and evaluation of sociocultural contexts, varying perspectives and narratives, and building of active, confident digital participation. The review suggests young children can develop foundational CDL skills, and implementing effective practices across policies, education, and home settings could yield long-term benefits. The ever-changing digital landscape necessitates further research and more comprehensive reviews.

Introduction: The dentist's main working area is the head and neck region, which is innervated by the cranial nerves. On a daily basis, dentists must administer local anaesthesia to ensure pain-free treatment and differentiate between dental pain and neuropathies to avoid mistreatment. Therefore, neuroanatomical training, especially on the cranial nerves, is of immense importance for clinical practice. In order to adopt the curriculum, it is essential to constantly evaluate the quality of the training and to investigate whether there is a correlation between the students' performance and the relevance of the subfields to their work. Material and methods: To address this issue, the results of MC exams in the neuroanatomy course for dental students at Charit & eacute;-Universit & auml;tsmedizin Berlin from winter semester 2014/2015 to winter semester 2019/2020 were analysed. Each question was assigned to a specific subfield of neuroanatomy. We then compared cranial nerves and cranial nerve nuclei (clinically relevant) with the remaining subfields (clinically less/not relevant) to investigate whether students performed better in anatomy subfields that are more aligned with the clinical practice of a dentist. We also conducted an anonymous survey (n=201) of the dental students. Results: From winter semester 2014/2015 to winter semester 2019/2020, students performed significantly (***, p< 0.001) better on the clinically relevant questions of the MC examination than on the less/not clinically relevant questions. However, when looking at each of the eleven semesters separately, only three semesters actually performed significantly better on the clinically relevant questions. Our survey also showed that students perceived the subfield of cranial nerves and cranial nerve nuclei to be the most relevant and studied it more intensively out of their own interest. Discussion: The study showed that students perceived the subfield of cranial nerves and cranial nerve nuclei to be the most relevant. However, there was no direct correlation between student performance and clinically relevant questions. Using student performance alone as an indicator of relevance is not optimal, as factors such as motivation to learn can have a significant impact. Conclusion: Greater clinical relevance influences what students learn more intensively out of their own interest, but does not influence the results of the MC examination in favour of the subspecialty. Based on the available evidence, it is recommended that the structure of the neuroanatomy course be reconsidered.

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100x higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; P < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n68) or above (group B, n65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m2) than that in group B (44.2 mL/min/1.73 m2; P-.0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of-4.282 mL/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.

Posttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose- lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-% TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM.

Regeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited. Here, we combined a previously developed purely architecture-driven biomaterial approach with the release of therapeutic metal ions from tailored silicate microparticles. The delivery platform was free of calcium phosphates (CaP) that are known to support IO but not EO and was employed for the release of lithium (Li), magnesium (Mg), strontium (Sr) or zinc (Zn) ions. We identified an ion-specific cellular response in which certain metal ions strongly enhanced cell recruitment into the material and showed superior chondrogenesis and deposition collagen II by human mesenchymal stromal cells (MSCs). At the same time, in some cases microparticle incorporation altered the mechanical properties of the biomaterial with consequences for cell-induced biomaterial contraction and scaffold wall deformation. Collectively, the results suggest that the incorporation of metal-doped silicate microparticles has the potential to further improve the bioactivity of architectured biomaterials for bone defect healing via EO. Statement of significance: Endochondral bone healing, a process that resembles embryonic skeletal development, has gained prominence in regenerative medicine. However, most therapeutic biomaterial strategies are not optimized for endochondral bone healing but instead target direct bone formation through IO. Here, we report on a novel approach to accelerate biomaterial-guided endochondral bone healing by combining cell-guiding collagen scaffolds with therapeutic metal-doped silicate microparticles. While other strategies, such as hypoxia-mimic drugs and iron-chelating biomaterials, have been documented in the literature before to enhance EO, our approach uniquely implements enhanced bioactivity into a previously developed biomaterial strategy for bone defect regeneration. Enhanced cell recruitment into the material and more pronounced chondrogenesis were observed for specific hybrid scaffold formulations, suggesting a high relevance of this new biomaterial for improved endochondral bone healing.

Magnesium as a biodegradable material offers promising results in recent studies of different maxillofacial fracture models. To overcome adverse effects caused by the fast corrosion of pure magnesium in fluid surroundings, various alloys, and surface modifications are tested in animal models. In specified cases, magnesium screws already appeared for clinical use in maxillofacial surgery. The present study aims to compare the bone healing outcome in a non-load-bearing fracture scenario of the forehead in sheep when fixed with standard-sized WE43 magnesium fixation plates and screws with plasma electrolytic oxidation (PEO) surface modification in contrast to titanium osteosynthesis. Surgery was performed on 24 merino mix sheep. The plates and screws were explanted en-bloc with the surrounding tissue after four and twelve weeks. The outcome of bone healing was investigated with micro-computed tomography, histological, immunohistological, and fluorescence analysis. There was no significant difference between groups concerning the bone volume, bone volume/ total volume, and newly formed bone in volumetric and histological analysis at both times of investigation. The fluorescence analysis revealed a significantly lower signal in the magnesium group after one week, although there was no difference in the number of osteoclasts per mm(2). The magnesium group had significantly fewer vessels per mm(2) in the healing tissue. In conclusion, the non-inferiority of WE43-based magnesium implants with PEO surface modification was verified concerning fracture healing under non-load-bearing conditions in a defect model. Statement of significance Titanium implants, the current gold standard of fracture fixation, can lead to adverse effects linked to the implant material and often require surgical removal. Therefore, degradable metals like the magnesium alloy WE43 with plasma electrolytic oxidation (PEO) surface modification gained interest. Yet, miniplates of this alloy with PEO surface modification have not been examined in a fracture defect model of the facial skeleton in a large animal model. This study shows, for the first time, the non-inferiority of magnesium miniplates compared to titanium miniplates. In radiological and histological analysis, bone healing was undisturbed. Magnesium miniplates can reduce the number of interventions for implant removal, thus reducing the risk for the patient and minimizing the costs.

The crustose cyanolichen Fuscopannaria frullaniae (syn. Moelleropsis nebulosa subsp. frullaniae ) is a poorly understood taxon that occurs on mosses and liverworts, described from eastern Canada and reported from the Iberian Peninsula, Macaronesia and the eastern USA. Originally placed in the genus Moelleropsis , the position of the species has been debated in the absence of sexual fruiting structures and, until now, DNA sequences from the fungal symbiont. We produced nine sequences from two fungal ribosomal loci from F. frullaniae collected at five different localities in Nova Scotia, Canada and North Carolina, USA. Initial BLASTn queries against public databases revealed high similarity between these sequences and basidiomycete sequences from the Dictyonema clade in Hygrophoraceae , specifically from the genus Acantholichen. We did not obtain ascomycete sequences from any locus or specimen. Phylogenetic analyses recovered the obtained sequences within the broader Acantholichen clade. We conclude that the lichen fungal symbiont is in fact a basidiomycete and introduce for it the new combination Acantholichen frullaniae. Acantholichen frullaniae is the first species of the genus to possess a granular, crustose thallus. The species lacks the characteristic, spiny, balloon-shaped cells called acanthohyphidia that are found in other species of the genus, though it possesses similar, albeit spineless cells on the surface of thallus granules; we suggest that these structures within the wider genus are homologous and represent spiny or smooth cystidia. Numerous samples yielded evidence of basidiospores and basidia produced from thallus granules, evident only after treatment with diluted potassium hydroxide, representing the first sexual structures reported in the genus. We discuss the possible reasons for this, as well as the ecology and threats to the species across its Canadian populations.

In this essay, I trace the genealogy of the “Miyawaki forest” or “Tiny Forest” concept by unpacking Akira Miyawaki’s treatises on natural vegetation and situating it within Zürich-Montpellier school of phytosociology. Drawing from impulses in more-than-human geography, I study Miyawaki projects that vouch to create fast, ‘self-sustaining’, close-range forests of native tree species in urban lands. By examining the maxims and techniques adopted in the Germanic study of plant communities, I showcase how such conservation ecologies align with functionalist-organicist traditions of the early 20th century. I pay particularly attention to the ecological concept of ‘potential natural vegetation’ (PNV) based on which species selection is carried out in the Miyawaki forest model. By tracing the notion of PNV – from its origin as an empirical phytosociological construct to providing ecological reinforcements of constructing a pure German vegetation during the Nazi regime – the article explains how right-wing ideologies were fueled by organicism in plant thinking. I showcase how such provincial epistemologies continue to pose reverberations onto the ‘nativist’ ethos of greening programs and urban forests today.

Acute central nervous system infection is highly lethal, yet the mechanisms by which intracellular bacteria infiltrate the brain remain unclear. Phagocytes are central to host defense, but how infected cells facilitate bacterial access to the brain is poorly defined. In this study, we characterize a CD36 + Fabp4 + Pparg + macrophage subset that mediates bacterial penetration of the brain without disrupting the blood–brain barrier. Biomechanical analysis reveals that CD36 + macrophages exhibit abundant protrusions and adhesion molecules, enabling resistance to blood flow shear stress and promoting endothelial adhesion. Metabolomic profiling reveals dysregulated lipid metabolism during neuroinvasion, with β-hydroxybutyrate promoting the differentiation and survival of CD36 + macrophages. Importantly, ketogenesis exacerbates symptoms during bacterial neuroinvasion, which could be halted by physiological glucose supplementation. Here, we show that intracellular bacteria exploit metabolically reprogrammed macrophages to access the brain, highlighting glycolipid metabolic homeostasis as a potential therapeutic target in bacterial neuroinvasion.

Climate change can intensify mosquito-borne disease risks through rising temperatures and more frequent extreme weather events. To mitigate effects of climate change, cities are adopting nature-based solutions, such as urban greening and rainwater management, yet their implications for vector-borne diseases and host community composition remain poorly understood. West Nile virus (WNV), an emerging mosquito-borne human pathogen in Europe, is primarily transmitted between birds and mosquitoes. Using mosquito sampling at five sites within a one-square-kilometre area in Berlin, Germany, we examined how urban land cover, including climate-resilient infrastructure, influences local WNV amplification over two mosquito seasons in 2023 and 2024. We found seasonal WNV infection rates of up to 4.8% in mosquitoes and identified fine-scale heterogeneity in infection risk. Residential areas and cemeteries exhibited the highest minimum infection rates per month (up to 15 and 21, respectively), whereas natural conversation and sponge city sites showed significantly lower rates (up to 4 and 13, respectively). These patterns were not explained by mosquito abundance or species composition but by habitat characteristics and avian host community structure. Our findings reveal that urban land cover shapes WNV infection risk and suggest that incorporating biodiversity restoration into nature-based solutions may serve as strategy for sustainable climate-resilient urban planning.

Dysregulated intracellular lipid metabolism emerged as a driver of heart failure (HF), a leading cause of death worldwide that is frequently caused by dilated cardiomyopathy (DCM). Yet, how defective lipid signaling destabilizes failing cardiomyocytes (CMs) at the molecular level remains elusive. We utilized induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), patient-derived heart tissue, and living adult CMs to elucidate lipid-dependent endoplasmic reticulum (ER) dysregulation in DCM and HF and identify new therapeutic targets. Lipidomics revealed abnormal intracellular cholesterol in iPSC-CMs carrying DCM-causing mutations in sarcomere proteins (tropomyosin; troponin T). Elevated cholesterol in CMs was found linked to abnormal ER architecture and dysfunction. STED microscopy, electron tomography, and biochemical analyses demonstrated that pathological ER remodeling and abnormal curvature are triggered by loss of ER-sarcomere/cytoskeleton contacts due to sarcomere misalignment in DCM CMs. Mechanistically, this signaling axis levers ER membrane dysfunctions and abnormal cholesterol levels via ER-sarcomere contact sites and operates in a bidirectional manner. Restoring intracellular cholesterol balance rescued ER membrane remodeling, sarcomere-ER contact site signaling, and sarcomere disarray in DCM iPSC-CMs. This ultimately improved the defective contractility of DCM iPSC-CMs, a key feature of failing CMs that contain a misaligned, dysfunctional sarcomere cytoskeleton. We validated this pathomechanism in end-stage DCM hearts and living atrial cardiomyocytes. Our findings suggest that intracellular cholesterol functions as a conserved ER membrane modulator and structural determinant across human CMs. Taken together, we present the lipidomic landscape of DCM and identify defective ER/cholesterol signaling as a disease driver whose therapeutic targeting rescues key functions in failing CMs.

Three-dimensional cell culture systems mimic native tissues via cell-cell and cell-matrix interactions, enabling functional models for regenerative medicine and drug research. As current biomaterials lack the hierarchical complexity of the extracellular matrix (ECM), the Matrix Evolution Consortium develops bioinspired, dynamic matrices from recombinant proteins and synthetic polymers, supported by advanced processing, biosensors for real-time monitoring, and in silico modeling.

With the expansion of high-speed railway networks and the increase in traffic density, delay propagation caused by unexpected events such as equipment failures, natural disasters, and safety incidents has become more pronounced. Traditional approaches, including mixed-integer programming and fireworks algorithm-based optimization, perform well under stable conditions but are less suitable for dynamic situations with multiple interacting trains. To address this issue, this paper proposes a dynamic scheduling framework based on multi-agents proximal policy optimization, with the goal of reducing train delays. In this framework, each train is treated as an independent agent within a distributed decision structure and makes decisions based on local observations described by 11-dimensional state features. A composite rewards mechanism is designed by combining punctuality incentives, safety headway constraints, speed control rules, and rewards and penalties related to minimum dwell time. A centralized training with decentralized execution strategy is adopted to improve coordination among agents. Results from case studies show that the method can effectively mitigate delay propagation under disruption conditions. The average station punctuality rate reaches 56.3%, the average terminal punctuality rate reaches 91.6%, and key trains achieve 100% terminal punctuality, indicating that the approach is applicable in complex railway systems.

Die duale Ausbildung zur/zum Fachangestellte/n für Medien- und Informationsdienste (FaMI) in Bibliotheken benötigt dringende Aktualisierungen. Die neue Ausbildungsverordnung soll kommen – doch gerade in der praktischen Ausbildung machen sich Ausbilder*innen bereits auf den Weg, zeitgemäß, zukunftsorientiert und attraktiv auszubilden. Nachhaltigkeit, Umweltschutz und Bildung für nachhaltige Entwicklung spielen hierbei eine bedeutsame Rolle. Welche „Future skills“ braucht es für den Berufsnachwuchs? Wie können neue Berufsfachkräfte als „Pioniere des Wandels“ Nachhaltigkeitsverständnis, Selbstwirksamkeit und Kreativität erlernen, um wirkungsvoll die „grüne Bibliothek von morgen“ zu gestalten? In Berlin gibt es seit drei Jahren regelmäßige Workshops für Auszubildende aus öffentlichen und wissenschaftlichen Bibliotheken. Mit welchen Inhalten, Methoden und Projektideen Nachhaltigkeit in der praktischen FaMI-Ausbildung gelingen kann, zeigt der folgende Praxisbericht aus dem Jahr 2026.