Kento Nakamura, Hajime Fukuoka, Akihiko Ishijima
et al.
Mutual information is a theoretically grounded metric for quantifying cellular signaling pathways. However, its measurement demands characterization of both input and output distributions, limiting practical applications. Here, we present alternative method that alleviates this requirement using dual reporter systems. By extending extrinsic-intrinsic noise analysis, we derive a mutual information estimator that eliminates the need to measure input distribution. We demonstrate our method by analyzing the bacterial chemotactic pathway, regarding multiple flagellar motors as natural dual reporters. We show the biological relevance of the measured information flow by comparing it with theoretical bounds on sensory information. This framework opens new possibilities for quantifying information flow in cellular signaling pathways.
Colorectal cancer (CRC) poses a major public health challenge due to its increasing prevalence, particularly among younger populations. Microsatellite instability-high (MSI-H) CRC and deficient mismatch repair (dMMR) CRC constitute 15% of all CRC and exhibit remarkable responsiveness to immunotherapy, especially with PD-1 inhibitors. Despite this, there is a significant need to optimise immunotherapeutic regimens to maximise clinical efficacy and patient quality of life whilst minimising monetary costs. To address this, we employ a novel framework driven by delay integro-differential equations to model the interactions among cancer cells, immune cells, and immune checkpoints. Several of these components are being modelled deterministically for the first time in cancer, paving the way for a deeper understanding of the complex underlying immune dynamics. We consider two compartments: the tumour site and the tumour-draining lymph node, incorporating phenomena such as dendritic cell (DC) migration, T cell proliferation, and CD8+ T cell exhaustion and reinvigoration. Parameter values and initial conditions are derived from experimental data, integrating various pharmacokinetic, bioanalytical, and radiographic studies, along with deconvolution of bulk RNA-sequencing data from the TCGA COADREAD and GSE26571 datasets. We finally optimised neoadjuvant treatment with pembrolizumab, a widely used PD-1 inhibitor, to balance efficacy, efficiency, and toxicity in locally advanced MSI-H/dMMR CRC patients. We mechanistically analysed factors influencing treatment success and improved upon currently FDA-approved therapeutic regimens for metastatic MSI-H/dMMR CRC, demonstrating that a single medium-to-high dose of pembrolizumab may be sufficient for effective tumour eradication while being efficient, safe and practical.
Kevin Troulé, Robert Petryszak, Martin Prete
et al.
Cell-cell communication is essential for tissue development, regeneration and function, and its disruption can lead to diseases and developmental abnormalities. The revolution of single-cell genomics technologies offers unprecedented insights into cellular identities, opening new avenues to resolve the intricate cellular interactions present in tissue niches. CellPhoneDB is a bioinformatics toolkit designed to infer cell-cell communication by combining a curated repository of bona fide ligand-receptor interactions with a set of computational and statistical methods to integrate them with single-cell genomics data. Importantly, CellPhoneDB captures the multimeric nature of molecular complexes, thus representing cell-cell communication biology faithfully. Here we present CellPhoneDB v5, an updated version of the tool, which offers several new features. Firstly, the repository has been expanded by one-third with the addition of new interactions. These encompass interactions mediated by non-protein ligands such as endocrine hormones and GPCR ligands. Secondly, it includes a differentially expression-based methodology for more tailored interaction queries. Thirdly, it incorporates novel computational methods to prioritise specific cell-cell interactions, leveraging other single-cell modalities, such as spatial information or TF activities (i.e. CellSign module). Finally, we provide CellPhoneDBViz, a module to interactively visualise and share results amongst users. Altogether, CellPhoneDB v5 elevates the precision of cell-cell communication inference, ushering in new perspectives to comprehend tissue biology in both healthy and pathological states.
The mechanical characterization of cell spheroids, one of the most widely used 3D biology models in vitro, is a hotspot of current research on the role played by the mechanical response of cells and tissues. The techniques proposed so far in the literature, while providing important scientific insights, require a specialized equipment and technical skills which are not usually available in cell biology facilities. Here, we present an innovative rheo-optical compression assay based on microscopy glass coverslips as the load applied to cell spheroids in standard cell culture plates and on image acquisition with an optical microscope or even a smartphone equipped with adequate magnification lenses. Mechanical properties can be simply obtained by correlating the applied load to the deformation of cell spheroids measured by image analysis. The low-cost, user-friendly features of the proposed technique can boost mechanobiology research making it easily affordable to any biomedical lab equipped with cell culture facilities.
The cytochrome bcl complex is an oligomeric membrane protein complex which is a component of the mitochondrial respiratory chain and of the electron transfer chains of numerous bacteria which use oxygen, nitrogen, and sulfur compounds as terminal electron acceptors. The cytochrome bcl complex also participates in the cyclic transfer of electrons to and from the photosynthetic reaction centers in anoxygenic photosynthetic bacteria. In all of these species the cytochrome bcl complex transfers electrons from ubiquinol to cytochrome c and links this electron transfer to translocation of protons across the membrane in which the bcl complex resides. The mechanism by which the cytochrome bcl complex links electron transfer to proton translocation is the protonmotive Q cycle (1). This protonmotive electron transfer is one of the most important mechanisms of cellular energy transduction, found in a phylogenetically diverse range of organisms (2). The purpose of this review is to explain the protonmotive Q cycle.
During the last four decades, digital technologies have disrupted many industries. Car control systems have gone from mechanical to digital. Telephones have changed from sound boxes to portable computers. But have the firms that digitized their products and services become more valuable than firms that didn’t? Here we introduce the construct of digital proximity, which considers the interdependent activities of firms linked in an economic network. We then explore how the digitization of products and services affects a company’s Tobin’s q—the ratio of market value over assets—a measure of the intangible value of a firm. Our panel regression methods and robustness tests suggest the positive influence of a firm’s digital proximity on its Tobin’s q. This implies that firms able to come closer to the digital sector have increased their intangible value compared to those that have failed to do so. These findings contribute a new way of measuring digitization and its impact on firm performance that is complementary to traditional measures of information technology (IT) intensity.
We investigate the suitability of toroidal microcavities for strong-coupling cavity quantum electrodynamics (QED). Numerical modeling of the optical modes demonstrate a significant reduction of the modal volume with respect to the whispering gallery modes of dielectric spheres, while retaining the high-quality factors representative of spherical cavities. The extra degree of freedom of toroid microcavities can be used to achieve improved cavity QED characteristics. Numerical results for atom-cavity coupling strength g, critical atom number No, and critical photon number no for cesium are calculated and shown to exceed values currently possible using Fabry-Perot cavities. Modeling predicts coupling rates g/2π exceeding 700 MHz and critical atom numbers approaching 10^(-7) in optimized structures. Furthermore, preliminary experimental measurements of toroidal cavities at a wavelength of 852 nm indicate that quality factors in excess of 108 can be obtained in a 50-µm principal diameter cavity, which would result in strong-coupling values of (g/(2π),n(0),N-0) = (86 MHz, 4.6 x 10^(-4), 1.0 x 10^(-3)).
Daniel Schindler, Ted Moldenhawer, Maike Stange
et al.
Amoeboid cell motility is essential for a wide range of biological processes including wound healing, embryonic morphogenesis, and cancer metastasis. It relies on complex dynamical patterns of cell shape changes that pose long-standing challenges to mathematical modeling and raise a need for automated and reproducible approaches to extract quantitative morphological features from image sequences. Here, we introduce a theoretical framework and a computational method for obtaining smooth representations of the spatiotemporal contour dynamics from stacks of segmented microscopy images. Based on a Gaussian process regression we propose a one-parameter family of regularized contour flows that allows us to continuously track reference points (virtual markers) between successive cell contours. We use this approach to define a coordinate system on the moving cell boundary and to represent different local geometric quantities in this frame of reference. In particular, we introduce the local marker dispersion as a measure to identify localized membrane expansions and provide a fully automated way to extract the properties of such expansions, including their area and growth time. The methods are available as an open-source software package called AmoePy, a Python-based toolbox for analyzing amoeboid cell motility (based on time-lapse microscopy data), including a graphical user interface and detailed documentation. Due to the mathematical rigor of our framework, we envision it to be of use for the development of novel cell motility models. We mainly use experimental data of the social amoeba Dictyostelium discoideum to illustrate and validate our approach.
We have demonstrated all-optical bistable switching operation of resonant-tunnelling devices with ultra-small high-Q Si photonic-crystal nanocavities. Due to their high Q/V ratio, the switching energy is extremely small in comparison with that of conventional devices using the same optical nonlinear mechanism. We also show that they exhibit all-opticaltransistor action by using two resonant modes. These ultrasmall unique nonlinear bistable devices have potentials to function as various signal processing functions in photonic-crystal-based optical-circuits.
Using a photoalignment technique with a sulphonic azo-dye as the surfactant aligning material, we fabricated electrically tunable liquid crystal q-plates with topological charge 0.5, 1.5 and 3 for generating optical vortex beams with definite orbital angular momentum (OAM) 1,3 and 6 per photon (in units of ¯h), respectively. We carried out several tests on our q-plates, including OAM tomography, finding excellent performances. These devices can have useful applications in general and quantum optics.
Hiroshi Sekoguchi, Yasushi Takahashi, T. Asano
et al.
We have investigated absorption losses due to surface water adsorbed on the surface of silicon heterostructure nanocavities with quality (Q) factors of several million. Measurements performed while changing the ambient humidity that the nanocavity is exposed to show that the Q value depends linearly on humidity. We also reveal that chemical treatment to change the degree of hydrophilicity of the surface results in a drastic increase of Q; we have obtained an experimental value of 9 million, which represents a new record for a heterostructure nanocavity. We analytically determine the absolute value of absorption loss by exploiting the degree of fluctuation of Q values between different samples.