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The telomeric valine–arginine dipeptide repeat protein changes state to diffuse staining in mitosis and represses in vitro translation

Translation of mammalian G-rich telomeric RNA via the Repeat Associated non-AUG (AUG, the mRNA start codon) mechanism can produce proteins consisting of long repeats of valine–arginine (VR) or glycine–leucine (GL) dipeptides. Their role in the cell has not been elucidated. Using confocal laser scanning microscopy combined with antibody staining we previously observed VR sequestered in punctate bodies and liquid droplets in the cytoplasm and nuclei of nonmitotic cells. Here, we report that cells in mitosis show diffuse VR staining throughout the cell, giving these cells a bright appearance. Upon mitotic enrichment using the cyclin-dependent kinase 1 (CDK1) inhibitor RO-3306. RO-3306, 100% of the mitotic cells showed the same diffuse staining. Antibody staining showed colocalization of VR and the L4 ribosomal protein in mitotic cells and in an in vitro firefly luciferase assay, VR depressed translation. Affinity purification combined with mass spectrometry identified ribosomal proteins as the major class of VR interacting proteins in U2OS cells including L4 along with tubulin and proteins related to neural degenerative diseases. This change from a sequestered, punctate state in interphase to dispersed diffuse staining in mitosis, and the affinity of VR for the L4 protein which lines the ribosomal exit tunnel suggests that an oligomerization change of VR may facilitate its involvement in inhibiting of global translation during mitosis. Extension to mouse embryonic cerebral cortical development showed clear staining in the ventricular zone where neural progenitor cells with a high mitotic index proliferate and in the cortical plate where new neurons settle.

The SMC Hinge is a Selective Gate for Obstacle Bypass

Abstract DNA loop-extruding SMC complexes play vital roles in genome maintenance and DNA immunity. However, how these ring-shaped DNA motors navigate large DNA-bound obstacles has remained unclear. Here, we demonstrate that a bacterial SMC Wadjet complex can efficiently bypass obstacles larger than the SMC coiled coil lumen when they are tethered to the extruded DNA by a single-stranded DNA or RNA linker. This bypass is mediated by the selective entrapment of the linker within the SMC hinge channel, which functions as an obligate gate—permitting passage of the linker while retaining double-stranded DNA stably inside the SMC ring and keeping associated obstacles outside. We further show that eukaryotic SMC hinges similarly accommodate ssDNA, and that the hinge is dispensable for loop extrusion by Wadjet, altogether suggesting that obstacle bypass represents the conserved, long-sought function of the SMC hinge toroid. By integrating hinge bypass with loop extrusion, we provide a mechanistic framework for how DNA-entrapping SMC complexes can generate chromosomal loops densely decorated with obstacles.

Occurrence, fate and ecological risks of phthalate esters and bisphenol A in coastal wastewater discharges

Age-related evolution of human gingiva towards a fibrotic-like connective phenotype

Musical intervention to reduce stress during botulinum toxin injection for spasticity: Protocol for a randomized controlled trial (MUSIBOT)

Introduction Botulinum toxin injections are a common treatment for managing spasticity resulting from central nervous system damage, including stroke, multiple sclerosis, and traumatic brain injury. However, the injections are associated with perceived pain, and many patients experience significant anticipatory stress regarding future sessions. The intensity of this stress varies among individuals. Music therapy, particularly receptive musical interventions structured around a U-shaped sequence, promotes progressive relaxation through distinct musical phases. This method has demonstrated efficacy in reducing pain and anxiety across various clinical contexts, including chronic and acute pain, Alzheimer’s disease, fibromyalgia, and neurologically mediated pain. Given the painful nature of botulinum toxin injections, this study proposes the use of receptive music therapy to improve patient tolerance of the procedure. We hypothesize that receptive musical intervention can reduce injection-induced stress in adults undergoing botulinum toxin treatment. To our knowledge, no studies have specifically investigated the effect of music therapy on stress related to botulinum toxin injections. We aim to conduct a prospective randomized (1:1) controlled trial to evaluate the impact of receptive music intervention on stress levels, measured via heart rate variability (HRV), during botulinum toxin injection sessions. The primary objective is to assess the effect of receptive musical intervention during botulinum toxin injections on injection-induced stress, measured by HRV. Secondary objectives include evaluating the intervention’s effects on pain intensity and anxiety levels. Methods and analysis Patient satisfaction following the music-assisted injection session will also be assessed. Additionally, the physician’s evaluation of the procedure and the patient’s perception of time during the session will be recorded. Ethics and dissemination All participants will provide written informed consent prior to enrollment. The study has received approval from the relevant institutional ethics committee (Comité de Protection des Personnes – ID: 25.00156.000468, Sud-Méditerranée IV, approved on 3 April 2025). Findings will be disseminated through peer-reviewed publications and presentations at scientific conferences. Trial registration ClinicalTrials.gov NCT06920524

Interactions between long- and short-term synaptic plasticity transform temporal neural representations into spatial

Information processing in the brain relies on the transmission of spikes through chemical synapses whose efficacies often depend on their recent firing history. While effects of such short-term plasticity on neural information processing have long been studied, it is unclear how interactions between short-term and long-term plasticity affect the learning abilities of neural networks. Here, we show that long-term changes to the short-term plasticity of individual synaptic connections enable neurons to learn to process temporal sequences of spikes as if they were spatial patterns. This mechanism allows neural circuits to flexibly increase their capacity and robustness at the expense of elevated spiking activity. We further show that neurons with plastic short-term plasticity can learn to discriminate between inputs on the basis of multineuronal spike correlations that extend over space and time. Our model fits recent electrophysiological measurements of short-term plasticity in the mouse and human neocortex and is consistent with the distributions of short-term plasticity induction and recovery. Our theory predicts that the learning rule observed at a given synaptic connection depends on the degree and type of short-term plasticity which is induced by the induction protocol for long-term plasticity.

Steering the catalyst structure and intermediates adsorption configuration during pulsed nitrate electroreduction

An integrated assessment of seed germination performance using classical and complementary metrics under abiotic stress

Multi-parameter pendulum tuned particle damper for vibration suppression in offshore wind turbine towers

Yield vulnerability of low-income smallholders to pollinator declines in Brazil is biome-dependent

Habitat loss and degradation, mainly driven by agricultural expansion and intensification, alter ecological processes, ecosystem services and human well-being at a global scale. Pollinator populations in degraded agricultural areas tend to collapse, which in turn can reduce the effective pollination of agricultural crops and food production, particularly in leading food producing countries, such as Brazil. We sought to understand how the vulnerability to pollinator failure and the economic value of pollination (EVP) are associated with farmland size, farmer income, habitat loss, and the size of the human footprint. We also examine socioeconomic predictors related to income inequality levels across Brazilian municipalities and phytogeographic domains. We show that 58% of all leading crops in Brazil are dependent to some degree on animal pollination, and agricultural production in 96.8% of all municipalities is at least partly vulnerable to pollinator failure. Soybean, coffee, cotton, tomato and cocoa accounted for 84% of the total economic valuation of cropland pollination in Brazil, with soybean alone representing more than half of this value. Including soybean, vulnerability and EVP were positively correlated with the Human Development Index (HDI), Gross Domestic Product (GDP), habitat loss, and farmland size. On the other hand, these key indicators were negatively associated with the human footprint and the proportion of low-income farmers. Excluding soybean, however, vulnerability increased across low-income municipalities, particularly across the Atlantic Forest, Cerrado, and Caatinga, revealing strong biome contrasts. Overall, EVP was consistently reduced in areas under heavier human footprint, suggesting that anthropogenic pressures reduce pollination benefits. Our results also show that soybean cultivation masks underlying social and regional disparities in agricultural vulnerability. Thus, the evaluation of pollination risks can be masked by commodity production. Enhancing ecological processes and promoting diversified, pollinator-friendly agriculture may strengthen food production, particularly for tropical low-income farmers in vulnerable regions, while contributing to ecosystem service provision and human well-being.

Breast cancer cell coculture induces normal lung fibroblast transition to CAFs, promoting tumor cell dormancy and therapy resistance

Cancer-associated fibroblasts (CAFs) shape the tumor microenvironment of primary breast tumors to promote tumor progression and therapy resistance. While the lung is a top metastatic site in breast cancer, the origins of lung metastasis-associated fibroblasts and their influence on disseminating tumor cell outgrowth and chemoresistance are poorly understood. Here, we demonstrate the applicability of 2-dimensional and 3-dimensional cocultures of primary human lung fibroblasts (LF) and breast cancer cells (BCC) as models of tumor–stromal interactions in lung metastatic breast cancer. Using these models, we find that BCC lines representing clinically relevant molecular subtypes differentially induce CAF-like phenotypes in primary LFs corresponding with their propensity for lung metastasis. Furthermore, we identify a mechanism by which juxtacrine signaling from LFs to triple negative breast cancer (TNBC) cells promotes expansion of prognostic dormant-like cell subpopulations and instigates autophagy-dependent therapy resistance via integrin and Janus kinase1/2 signaling. A high content kinase inhibitor compound library screen using this model identifies vacuolar protein sorting 34 as a therapeutic vulnerability unique to BCC-LF interaction whose inhibition can resensitize TNBC cells to chemotherapy and relieve LF-mediated extrinsic therapy resistance. Therefore, we propose coculture of primary human LFs and BCC as a reductionist model of interactions between tumor cells and lung-resident stroma and a tool for therapeutic and mechanistic discovery in lung metastatic breast cancer.

Hierarchical ground-state crystals underlying Hertzian quasicrystals

Abstract As a simple physics model for crystal and quasicrystal formation, the Hertzian potential describes the interaction between two soft-core colloidal particles. However, explaining why quasicrystals emerge in such a minimal model remains a theoretical challenge. Here, using analytically exact approaches, we reveal multiple layers of hierarchical crystal patterns that serve as the energy ground states underlying quasicrystals found by computer simulations. Our findings offer a new perspective on quasicrystal formation.

Asymmetry in snow-water nexus in mountain areas mainly governed by meteorological seasonal changes

Abstract Despite the importance of snow cover and related streamflow changes in mountain catchments worldwide, hitherto the quantification of their mutual variability has not been addressed at this scale. This work utilizes satellite and ground observations spanning the last two decades to investigate the nexus between snow cover and streamflow across 548 mountain catchments globally. The results show that around 5% of these catchments are simultaneously affected by significant trends in both variables. This happened mainly in the Andes Cordillera, where snow season ends 28 days earlier, with a snow cover area reduction of about 15%, and a decrease in annual streamflow of 67 m 3 /s. Moreover, in 16% of the catchments, significant changes occur only in one of the variables. This asymmetric behaviour was connected with significant changes in a specific season. When the most affected season is summer, with marked temperature increase, snow changes are not reflected in streamflow, as the latter mainly depends on spring snowmelt, as observed in the European Alps. When there is an increase in winter solid precipitation, this may not be reflected in yearly snow cover changes but can impact the resulting streamflow, as shown in the western North American catchments.

Risky sexual behavior and its associated factors among employees in industrial park, Northeast, Ethiopia

Correction: Contrastive learning enhanced pseudo-labeling for unsupervised domain adaptation in person re-identification

Longitudinal transformation of mitochondrial metabolism during neurogenesis

Neural stem cells (NSCs) are valuable in the quest to conquer neurodegenerative diseases due to their capability to reconstruct the damaged neuronal networks. However, deep understanding of the intercellular signaling mechanism controlling the lineage and fate of the stem cells is required before potential clinical applications. Here, we applied nondestructive and label-free electrochemical methods for the longitudinal tracking of NSC respiratory metabolism. Sharp change in the oxygen utilization pattern was observed concomitant to stemness loss and onset of differentiation, suggesting metabolic reprogramming in the transition. Intra- and extracellular profiling of mitochondrial metabolites revealed molecular preference in the extracellular transport rates. Electrochemical emulation of the metabolite release pattern induced acceleration of neurite growth in nearby cells, suggesting paracrine signaling system mediated by mitochondrial metabolites.

Design principles of practical industrial-scale layered oxide cathodes with air/water stability for sustainable sodium-ion batteries

Correction: Impact of glibenclamide pretreatment on outcomes in acute ischemic stroke patients with type 2 diabetes: a retrospective case–control study

Electric fields unlock a transient vulnerability window for vancomycin-based treatment of staphylococcal biofilms

Abstract Bacterial biofilms pose a significant challenge to antibiotic treatment. Conventional therapeutic interventions often fail to effectively eradicate mature biofilms due to the protective extracellular matrix and altered physiological states of the embedded bacteria. In this study, we show that low-intensity sinusoidal electric fields induce a time-limited window of vulnerability in mature Staphylococcus aureus biofilms, increasing their susceptibility to vancomycin. In particular, the simultaneous application of electric fields and vancomycin during a transient vulnerability window results in a potentiated effect, leading to an approximately 3-log 10 reduction in culturable cell counts relative to untreated controls. Conversely, the effectiveness of the antibiotic is reduced when vancomycin is administered after the cessation of the time-limited vulnerability window associated to the electrical stimulation, indicating a time-dependent reversibility of the electrical effect on the biofilm. These results suggest that the electric fields can create a critical phase of increased susceptibility to antibiotics, establishing a bioelectric strategy for biofilm control and highlighting the importance of treatment timing.

Evaluation of potentially toxic elements and ecological risks associated with environmental liabilities in Tacna, Peru

Mining environmental liabilities (MELs) are abandoned deposits resulting from extractive activities that pose a high risk of contamination and remain an unresolved challenge for authorities worldwide. This study evaluated the contamination levels of potentially toxic elements (PTEs) and their associated ecological risks in MELs, using multiple environmental indices. Analyses were performed following the EPA 6020A method with acid digestion and inductively coupled plasma mass spectrometry (ICP-MS), while free cyanide and hexavalent chromium were determined using the EPA 9013A and EPA 7199 methods, respectively. The results revealed elevated concentrations of arsenic (1,102 mg/kg), cadmium (271 mg/kg), lead (15,961 mg/kg), and free cyanide (64 mg/kg), which exceeded regulatory standards by a considerable margin. Statistically significant differences were observed across the sites (p < 0.05). In addition, the presence of flora, fauna, rivers, and rural communities in proximity to these abandoned mining sites amplifies both ecological and social risks. The applied indices consistently indicated severe levels of contamination and high ecological risk across all areas evaluated. Although no statistically significant differences were found in some indices (p > 0.05), the magnitude of the recorded values remains ecologically relevant. Notably, each index has its own interpretative scale, allowing for an independent and robust evaluation of contamination severity and its potential ecological implications. Principal Component Analysis (PCA) revealed multiple sources of pollution, while Spearman correlation analysis identified strong associations among PTEs, suggesting common environmental dispersion pathways. This research provides a critical preliminary assessment of the risks associated with these environmental legacies and emphasizes the urgent need for remediation efforts at both local and global scales. The current lack of action is largely attributed to the absence of comprehensive baseline assessments. The findings underscore the importance of prioritizing their management through sustainable strategies and international policies to mitigate environmental impacts.