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Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology
Abstract Synaptic dysfunction in Alzheimer’s disease (AD) may drive synapse loss and cognitive impairment. Whether AD-related synaptic pathophysiology occurs globally, or in specific synapses, is unclear. We investigate in vivo AD-related synaptic dysfunction during early-stage amyloidosis in App NL-G-F mice. We find reduced presynaptic GABAergic proteins at c-Fos-positive excitatory neurons and increased calcium-mediated activity at excitatory and inhibitory neuronal assemblies. In vivo synaptic structure/function imaging finds reduced density and calcium-mediated activity of GABAergic axonal boutons. Rather than occurring globally, reduced synaptic activity is focused at GABAergic boutons strongly coupled to population activity in the amyloid microenvironment. The selective weakening of population-coupled synaptic activity also occurs in excitatory dendritic spines. Spatial transcriptomics finds parvalbumin-positive inhibitory neurons show differential gene expression associated with downregulated GABAergic synaptic transmission at early stages. We propose that early-stage AD-related synaptic pathophysiology is focused at population-coupled synapses, with molecular measures implicating abnormal synaptic processing as an early-stage feature in parvalbumin-positive interneurons.
A joint modeling framework for time-to-fatigue prediction with a single wearable sensor biomarker
Elucidating activity-stability trade-offs in nano-fingerprint carbon anchoring single atoms and clusters in oxygen reduction reaction
Cognitive biotypes identified through ECG-derived workload and behavioral accuracy
Tudor domain-containing protein 9-targeting siRNA nanoparticles alleviate Pseudomonas aeruginosa lung injury in preclinical models by promoting neutrophil cuproptosis
Incremental learning approach for semantic segmentation of skin histology images
Concise construction of β-branched aromatic D-amino acids via transaminase-catalyzed dynamic kinetic resolution
The influence of non-oceanic forces on the mean sea level of the Brazilian coast: a bivariate and multivariate approach
African inland wetland area on the rise during the 21st century
Abstract Wetlands face threats from climate change and human activities worldwide, yet the status of African wetlands remains unknown. This study mapped African wetlands and assessed area loss, drivers, and future trends under climate change using 270,000 sampling points, 810,000 Landsat images, and soil moisture data from 14 CMIP6 models. The results reveal no large-scale loss of wetlands in Africa from 1984 to 2021 (0.51% net loss), with the loss concentrated in coastal areas (9.64% net loss), while inland wetlands show a slight increase in area (0.50% net increase). A comparison of the time series of wetland area and related drivers showed that the change of inland wetland area is closely related to climate change, and human activities have exacerbated the loss of coastal wetlands. TOPMODEL projections suggest an upward trend in inland wetland area by 2100, but uncertainty persists and inland wetlands remain at risk of loss in the future.
A hybrid machine learning approach for reliably predicting surface roughness in CNC turning operations
The genetic basis of dermatophytosis skin infection susceptibility
Abstract Dermatophytosis is a fungal infection affecting keratinized tissues such as skin, nails, and hair, presenting as red and itchy patches, nail thickening, or hair loss. It affects around 20% of the global population but the genetic architecture remains poorly understood. We performed a genome-wide association meta-analysis of over 250,000 cases and 1.37 million controls from FinnGen, Estonian Biobank, UK Biobank, and the Million Veteran Program and identified 30 genome-wide significant loci, including seven missense variants and two loci in high linkage disequilibrium with missense variants. Top associations were near ZNF646 , HLA-DQB1 , FLG , FTO , SLURP2 , and KRT77 . Additionally, dermatophytosis subtype analyses revealed 44 signals. Our results highlight the role of disrupted keratin biology, skin barrier defects, immune dysfunction, and obesity in dermatophytosis risk. We also observed genetic overlap with other skin conditions and obesity-related traits, providing insights into disease mechanisms and potential targets for prevention and treatment.
Object tracking algorithm based on deformable attention mechanism
Abstract Occlusion, sudden illumination changes, and rapid motion in complex scenes severely degrade the robustness of existing object tracking methods. To address this issue, this paper proposes a novel object tracking algorithm that integrates a deformable attention mechanism. The method first embeds a deformable attention module into the ResNet-18 feature extraction network to enable adaptive enhancement of target key features. Second, the method adopts an improved Bidirectional Feature Pyramid Network as the feature fusion module to enhance the representational capability of multi-scale features. Finally, the method incorporates a dynamic Kalman filtering prediction module to improve the algorithm’s adaptability to changes in the target’s motion state and its continuous tracking capability. Experimental results show that the improved feature extraction network achieves an average overlap rate and success rate of 61.5% and 68.4%, respectively, on the GOT-10k dataset, with a computational load of only 1.96 GFLOPs and an increase of only 0.23 M in parameters. On the MOT20 dataset, the proposed object tracking network achieves a Multiple Object Tracking Accuracy of 77.5%, an Identity F1 Score of 77.0%, with 54.6% Majority of Tracked Trajectories and 12.5% Majority of Lost Trajectories. Its tracking performance surpasses that of the compared object tracking algorithms. These results confirm the efficacy of the Deformable Attention Mechanism and present a robust solution for complex dynamic tracking scenarios.
Phosphorylation of WDR48 by phototropins drives starch degradation to promote stomatal opening
Abstract Plant stomata open in response to blue light under a background of red light. Red light induces starch accumulation through guard cell photosynthesis, whereas blue light causes rapid starch degradation via the activation of plasma membrane H + -ATPase through phosphorylation of BLUS1 by phototropins, thus promoting stomatal opening. However, how phototropins mediate starch degradation remains unclear. In this study, we identified WD-repeat protein 48 (WDR48), which is essential for starch degradation. Phosphoproteomic analysis revealed that WDR48 was phosphorylated in response to blue light. Mutation of WDR48 impaired starch degradation and stomatal opening by blue light. Phototropins interacted with and phosphorylated WDR48. WDR48 and BLUS1 constituted separate signalling pathways required for starch degradation. We propose that the coordinated control of starch synthesis by red light and its degradation by blue light signalling through WDR48 and BLUS1 is a key mechanism for stomatal opening by red and blue light.
Complementary neuroprotective effects of semaglutide and papaya in diabetic encephalopathy via antioxidant and insulin-signaling pathways
Fragmentomic liquid biopsy enables early breast cancer detection, molecular subtyping and lymph node assessment
VolE: A point-cloud framework for food 3D reconstruction and volume estimation
Upwind electromigration of sub-10-nm metallic nano-interconnects
Preliminary insights into gut microbiome shifts as screening proxy for MASLD disease progression
Reflections on bio-based PET and plastic waste management: a responsible research and innovation approach
Abstract Plastics drive twin crises: persistent pollution and greenhouse gas emissions. Bio-based approaches using enzymes and microorganisms to depolymerise plastics and valorise monomers show promise but raise societal, ethical and regulatory questions central to Responsible Research and Innovation (RRI). In this Perspective, we reflect on RRI implications of bio-based plastic degradation, informed by stakeholder discussions across the plastics value chain and public engagement. We identify broad support alongside concerns about scalability, interaction with existing recycling, governance and containment of genetically modified organisms, management of additives and contaminants, and the roles of regulation and economic incentives in enabling adoption.