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Operating principles of interconnected feedback loops driving cell fate transitions
Interconnected feedback loops are prevalent across biological mechanisms, including cell fate transitions enabled by epigenetic mechanisms in carcinomas. However, the operating principles of these networks remain largely unexplored. Here, we identify numerous interconnected feedback loops implicated in cell lineage decisions, which we discover to be the hallmarks of lower- and higher-dimensional state space. We demonstrate that networks having higher centrality nodes have restricted state space while those with lower centrality nodes have higher dimensional state space. The topologically distinct networks with identical node or loop counts have different steady-state distributions, highlighting the crucial influence of network structure on emergent dynamics. Further, regardless of topology, networks with autoregulated nodes exhibit multiple steady states, thereby “liberating” network dynamics from absolute topological control. These findings unravel the design principles of multistable networks implicated in fate decisions and can have crucial implications in engineering or comprehending multi-fate decision circuits.
A computational spectrometer for the visible, near, and mid-infrared enabled by a single-spinning film encoder
Computational spectrometers enable low-cost, in-situ, and rapid spectral analysis, with applications in chemistry, biology, and environmental science. Traditional filter-based spectral encoding approaches typically use filter arrays, complicating the manufacturing process and hindering device consistency. Here we propose a computational spectrometer spanning visible to mid-infrared by combining the Single-Spinning Film Encoder (SSFE) with a deep learning-based reconstruction algorithm. Optimization through particle swarm optimization (PSO) allows for low-correlation and high-complexity spectral responses under different polarizations and spinning angles. The spectrometer demonstrates single-peak resolutions of 0.5 nm, 2 nm, 10 nm, and dual-peak resolutions of 3 nm, 6 nm, 20 nm for the visible, near, and mid-infrared wavelength ranges. Experimentally, it shows an average MSE of 1.05 × 10⁻³ for narrowband spectral reconstruction in the visible wavelength range, with average center-wavelength and linewidth errors of 0.61 nm and 0.56 nm. Additionally, it achieves an overall 81.38% precision for the classification of 220 chemical compounds, showcasing its potential for compact, cost-effective spectroscopic solutions.
Approaching maximum resolution in structured illumination microscopy via accurate noise modeling
Biological images captured by microscopes are characterized by heterogeneous signal-to-noise ratios (SNRs) due to spatially varying photon emission across the field of view convoluted with camera noise. State-of-the-art unsupervised structured illumination microscopy (SIM) reconstruction methods, commonly implemented in the Fourier domain, often do not accurately model this noise. Such methods therefore suffer from high-frequency artifacts, user-dependent choices of smoothness constraints making assumptions on biological features, and unphysical negative values in the recovered fluorescence intensity map. On the other hand, supervised algorithms rely on large datasets for training, and often require retraining for new sample structures. Consequently, achieving high contrast near the maximum theoretical resolution in an unsupervised, physically principled manner remains an open problem. Here, we propose Bayesian-SIM (B-SIM), a Bayesian framework to quantitatively reconstruct SIM data, rectifying these shortcomings by accurately incorporating known noise sources in the spatial domain. To accelerate the reconstruction process, we use the finite extent of the point-spread-function to devise a parallelized Monte Carlo strategy involving chunking and restitching of the inferred fluorescence intensity. We benchmark our framework on both simulated and experimental images, and demonstrate improved contrast permitting feature recovery at up to 25% shorter length scales over state-of-the-art methods at both high- and low SNR. B-SIM enables unsupervised, quantitative, physically accurate reconstruction without the need for labeled training data, democratizing high-quality SIM reconstruction and expands the capabilities of live-cell SIM to lower SNR, potentially revealing biological features in previously inaccessible regimes.
Evolution of temporomandibular joint reconstruction: from autologous tissue transplantation to alloplastic joint replacement
The reconstruction of the temporomandibular joint presents a multifaceted clinical challenge in the realm of head and neck surgery, underscored by its relatively infrequent occurrence and the lack of comprehensive clinical guidelines. This review aims to elucidate the available approaches for TMJ reconstruction, with a particular emphasis on recent groundbreaking advancements. The current spectrum of TMJ reconstruction integrates diverse surgical techniques, such as costochondral grafting, coronoid process grafting, revascularized fibula transfer, transport distraction osteogenesis, and alloplastic TMJ replacement. Despite the available options, a singular, universally accepted ‘gold standard’ for reconstructive techniques or materials remains elusive in this field. Our review comprehensively summarizes the current available methods of TMJ reconstruction, focusing on both autologous and alloplastic prostheses. It delves into the differences of each surgical technique and outlines the implications of recent technological advances, such as 3D printing, which hold the promise of enhancing surgical precision and patient outcomes. This evolutionary progress aims not only to improve the immediate results of reconstruction but also to ensure the long-term health and functionality of the TMJ, thereby improving the quality of life for patients with end-stage TMJ disorders.
Curiosity shapes spatial exploration and cognitive map formation in humans
Cognitive maps are thought to arise, at least in part, from our intrinsic curiosity to explore unknown places. However, it remains untested how curiosity shapes aspects of spatial exploration in humans. Combining a virtual reality task with indices of exploration complexity, we found that pre-exploration curiosity states predicted how much individuals spatially explored environments, whereas markers of visual exploration determined post-exploration feelings of interest. Moreover, individual differences in curiosity traits, particularly Stress Tolerance, modulated the relationship between curiosity and spatial exploration, suggesting the capacity to cope with uncertainty enhances the curiosity-exploration link. Furthermore, both curiosity and spatial exploration predicted how precisely participants could recall spatial-relational details of the environment, as measured by a sketch map task. These results provide new evidence for a link between curiosity and exploratory behaviour, and how curiosity might shape cognitive map formation.
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