搜索结果：Journal of cell communication and signaling

Reproducibility is a current concern for everyone involved in the conduct and publication of biomedical research. Recent attempts testing reproducibility, particularly the reproducibility project in cancer biology published in elife (https://elifesciences.org/collections/9b1e83d1/reproducibility-project-cancer-biology), have exposed major difficulties in repeating published preclinical experimental work. It is thought that some of these difficulties relate to uncertainty about the provenance of tools, lack of clarity in methodology and use of inappropriate approaches for analysis; the latter particularly related to untoward manipulation of images. In the past, some of these so-called untoward practices were considered the ‘norm’; however, today, the landscape is different. The expectations, not only of the readers of the published scientific word but also of the publishers and funders of research, have changed. This collective group now expects that any published data should be reproducible; but for this to be possible, experimental detail, confirmation of selectivity and quality of reagents/tools, analytical and statistical methods used need to be described adequately. Two powerful methodologies often used to support researchers' findings allow the detection of changes in protein expression, that is, immunoblotting (widely known as Western blotting) and immunohistochemistry. Undeniably, as a result of unintentional mistakes (often related to lack of antibody specificity; Baker, 2015), but, in some cases, deliberate alterations and questionable interpretations of results, the use of these two methods has led to many high profile retractions. Indeed, such images have driven the retractions that have occurred in BJP over the last two years. Today, immunoblotting and immunohistochemistry serve as primary methodologies for the detection and quantification of molecular signalling pathways and identification of therapeutic targets. This necessitates clear guidance for the application of these techniques, the need for controls (both positive and negative) and the most appropriate methods for quantification. Indeed, this need has spawned a number of initiatives to support researchers in assessing the validity of antibody resources including antibodypedia (Bjorling and Uhlen, 2008) and the resources available within ‘The Human Protein Atlas’ (Thul et al., 2017). The aim of this article is to outline the rationale for, and the expectations of, the BJP with respect to work published in the Journal that includes immunoblotting or immunohistochemical data. In creating these guidelines, our aim is to reduce potential misinterpretations and to maximise the communication and transparency of essential information, particularly with respect to the methodologies employed. We have generated the guidelines below for the benefit of authors, editors and reviewers. While we recognise other recently published guidelines (Uhlen et al., 2016) and indeed we have incorporated some of the advice provided in such reports, we focus, here, on the evidence required for publication in BJP. These guidelines join a series published in BJP regarding the reporting of animal experiments through adoption of the ARRIVE guidelines (McGrath et al., 2015; McGrath and Lilley, 2015), experimental design and analysis (Curtis et al., 2015) and data sharing and presentation (George et al., 2017) in preclinical pharmacology. We would be delighted if other journals were to also use these guidelines. If an antibody has been characterised previously, a citation must be included. This characterization should fulfil the requirements detailed in the recent guidelines generated by ‘The International Working Group for Antibody Validation’ and should take the form of at least, but preferably more than, one of the ‘five conceptual pillars of antibody validation’ described in the guidelines (Uhlen et al., 2016). We also ask authors to check currently available databases for known issues with selectivity. Currently, we highly recommend the NIH-established Research Resource Identification Protocol (RRID) at https://scicrunch.org/resources/Cell%20Lines/search, which provides a unique identifier for the antibody that enables reproducibility studies through clear indication of provenance. Although encouraged, the inclusion of an RRID is not currently mandatory for BJP; we envisage that a similar level of individualization will become essential for publication in the near future. To support the validity of conclusions emanating from immunoblotting or immunohistochemical observations (as with the majority of biological assays), it is important to conduct both positive and negative controls – although for some proteins, certain positive and negative controls are unknown or such materials are not available, thereby precluding such assessments. However, there are a number of other ‘method’ controls that are always possible and which should be included in assay protocols. We recognise that there may be no perfect control that provides confidence beyond doubt (Torlakovic et al., 2015). In this digital age, a growing concern amongst the scientific community is that images for publication are not being accurately presented, that is, the problem of unintentional and/or inappropriate manipulation of images (Cromey, 2010). For example, while it is usually acceptable to crop an image to simplify the information, choosing to crop out oversaturated regions and/or areas/bands displaying non-specific immunoreactivity is not acceptable. BJP requires submission of full immunoblot scans and immunohistochemical/fluorescent images, from which figures have been generated. These scans/images should be included as an additional file for the review process and will be used by the Editors and reviewers when assessing the manuscript, but need not be published. In instances where uncertainty occurs regarding image compilation and assembly during the review process, the BJP Editorial Office makes use of freely available Office of Research Integrity Forensic tools (https://ori.hhs.gov/forensic-tools), developed by the US Department of Health and Human Services. Conforming to these stipulations will ensure that reviewers and readers can confirm that the band identified is at the correct molecular size (or allow some interpretation of post-translational modifications, for example) and to determine the selectivity of the antibody used. For any antibody (including secondary antibodies) used, the Methods section should include the following:

Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of cancer. Further research is needed to unravel the complex mechanisms underlying oxidative stress-related pathways and to develop effective strategies that can be translated into clinical applications for the management and treatment of cancer. Video Abstract.

Abstract Understanding global communications among cells requires accurate representation of cell-cell signaling links and effective systems-level analyses of those links. We constructed a database of interactions among ligands, receptors and their cofactors that accurately represents known heteromeric molecular complexes. Based on mass action models, we then developed CellChat, a tool that is able to quantitively infer and analyze intercellular communication networks from single-cell RNA-sequencing (scRNA-seq) data. CellChat predicts major signaling inputs and outputs for cells and how those cells and signals coordinate for functions using network analysis and pattern recognition approaches. Through manifold learning and quantitative contrasts, CellChat classifies signaling pathways and delineates conserved and context-specific pathways across different datasets. Applications of CellChat to several mouse skin scRNA-seq datasets for embryonic development and adult wound healing shows its ability to extract complex signaling patterns, both previously known as well as novel. Our versatile and easy-to-use toolkit CellChat and a web-based Explorer ( http://www.cellchat.org/ ) will help discover novel intercellular communications and build a cell-cell communication atlas in diverse tissues.

We generated a computational approach to analyze the biomechanics of epithelial cell aggregates, either island or stripes or entire monolayers, that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a 3-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical crosstalk as well as distribution of principal stress in cells within epithelial cell aggregates. By mak

Ligand-receptor interactions constitute a fundamental mechanism of cell-cell communication and signaling. NicheNet is a well-established computational tool that infers ligand-receptor interactions that potentially regulate gene expression changes in receiver cell populations. Whereas the original publication delves into the algorithm and validation, this paper describes a best practices workflow cultivated over four years of experience and user feedback. Starting from the input single-cell expression matrix, we describe a "sender-agnostic" approach which considers ligands from the entire microenvironment, and a "sender-focused" approach which only considers ligands from cell populations of interest. As output, users will obtain a list of prioritized ligands and their potential target genes, along with multiple visualizations. In NicheNet v2, we have updated the data sources and implemented a downstream procedure for prioritizing cell-type-specific ligand-receptor pairs. Although a standard NicheNet analysis takes less than 10 minutes to run, users often invest additional time in making decisions about the approach and parameters that best suit their biological question. This paper

Collective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in

Multi-nucleated cells exist in all domains of life, ranging from animals, plants and fungi to single-celled organisms such as the slime mold Physarum polycephalum. The large cell size, in the case of Physarum reaching centimeters and more, challenges the coordination of nuclei activity as signals need to cross large distances. In search for a mechanism for fast long-ranged communication among nuclei, we quantify nuclei dynamics and cytoplasmic flows in Physarum's tubular network. We observe nuclei in two interchangeable, dynamic states: mobile, flowing within the cytoplasmic shuttle flow, or trapped in the tube's porous cell cortex. As we find nuclei to accumulate at the tube's inner fluid-porous interface we theoretically explore and confirm, with physiological parameters, that slowing down of mobile nuclei during flow is sufficient for diffusible signal exchange between mobile and trapped nuclei. We analytically derive that communication akin to pigeon-post with mobile nuclei serving as pigeons shuttling between trapped nuclei acting as waypoints, gives rise to signaling velocities that account for the rapid intracellular reorganization observed in Physarum. Since signal transfer

Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased), ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

The crawling motility of many eukaryotic cells is driven by filamentous actin (F-actin), and regulated by a network of signaling proteins and lipids (including small GTPases). The tangle of positive and negative feedback loops gives rise to various experimentally observed dynamic patterns (``actin waves''). Here we consider a recent prototypical model for actin waves in which F-actin exerts negative feedback onto a GTPase. Guided by recent numerical PDE bifurcation analysis in Hughes (2025) and Hughes et al (2026), we explore cell shapes and motility associated with polar, oscillatory, and traveling waves solutions of a mass-conserved partial differential equation (PDE) model. We use Morpheus (cellular Potts) simulations to investigate the implications of such regimes of behavior on the shapes and motion of cells, and on transitions between modes of behavior. The model demonstrates various cell states, including resting (spatially uniform GTPase), polar cells (static ``zones'' of GTPase), and traveling waves along the cell edge. In some parameter regimes, such states can coexist, so that cells can transition from one behavior to another in response to noisy stimuli.

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

Prior studies on mixed near-field and far-field communications have focused exclusively on single-cell scenarios, where both near-field and far-field users are served by the same base station (BS), leading to intra-cell mixed-field interference. In this paper, we consider a more general and practical multi-cell mixed-field scenario consisting of multiple cells, each serving multiple users, thus resulting in more complex inter-cell mixed-field interference. To address this new challenge, we propose leveraging rotatable antenna (RA) technology to enhance multi-cell mixed-field communication performance by exploiting the additional spatial degree-of-freedom introduced by RA rotation to mitigate interference in an efficient way. Specifically, we study an RA-enabled multi-cell mixed-field communication system in which each BS is equipped with an RA array to serve its associated users. We formulate a network-wide sum-rate maximization problem that jointly optimizes the transmit beamforming and the rotation angles of the RA arrays, subject to per-BS power constraints and admissible array rotation limits. To gain useful insights into the role of RAs in multi-cell mixed-field communications

We compare the network of aggregated journal-journal citation relations provided by the Journal Citation Reports (JCR) 2012 of the Science and Social Science Citation Indexes (SCI and SSCI) with similar data based on Scopus 2012. First, global maps were developed for the two sets separately; sets of documents can then be compared using overlays to both maps. Using fuzzy-string matching and ISSN numbers, we were able to match 10,524 journal names between the two sets; that is, 96.4% of the 10,936 journals contained in JCR or 51.2% of the 20,554 journals covered by Scopus. Network analysis was then pursued on the set of journals shared between the two databases and the two sets of unique journals. Citations among the shared journals are more comprehensively covered in JCR than Scopus, so the network in JCR is denser and more connected than in Scopus. The ranking of shared journals in terms of indegree (that is, numbers of citing journals) or total citations is similar in both databases overall (Spearman's \r{ho} > 0.97), but some individual journals rank very differently. Journals that are unique to Scopus seem to be less important--they are citing shared journals rather than bein

This paper presents a software platform, named BiNS2, able to simulate diffusion-based molecular communications with drift inside blood vessels. The contribution of the paper is twofold. First a detailed description of the simulator is given, under the software engineering point of view, by highlighting the innovations and optimizations introduced. Their introduction into the previous version of the BiNS simulator was needed to provide to functions for simulating molecular signaling and communication potentials inside bounded spaces. The second contribution consists of the analysis, carried out by using BiNS2, of a specific communication process happening inside blood vessels, the atherogenesis, which is the initial phase of the formation of atherosclerotic plaques, due to the abnormal signaling between platelets and endothelium. From a communication point of view, platelets act as mobile transmitters, endothelial cells are fixed receivers, sticky to the vessel walls, and the transmitted signal is made of bursts of molecules emitted by platelets. The simulator allows evaluating the channel latency and the footprint on the vessel wall of the transmitted signal as a function of the t

Aim. To study the dynamics of auto-oscillations arising at the level of enzyme-substrate interaction in a cell and to find the conditions for the self-organization and the formation of chaos in the metabolic process. Methods. A mathematical model of the metabolic process of steroids transformation in Arthrobacter globiformis. The mathematical apparatus of nonlinear dynamics. Results. The bifurcations resulting in the appearance of strange attractors in the metabolic process are determined. The projections of the phase portraits of attractors are constructed for some chosen modes. The total spectra of Lyapunov's indices are calculated. The structural stability of the attractors obtained is studied. By the general scenario of formation of regular and strange attractors, the structural-functional connections in the metabolic process in the cell are found. Their physical nature is investigated. Conclusions. The presented model explains the mechanism of formation of auto-oscillations observed in the A. globiformis cells and demonstrates a possibility of the mathematical modeling of metabolic processes for the physical explanation of the self-organization of a cell and its vital activity

The amino sugar N-acetylglucosamine (GlcNAc) is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli respond to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the post-translational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this review.

As the standardization of 5G solidifies, researchers are speculating what 6G will be. The integration of sensing functionality is emerging as a key feature of the 6G Radio Access Network (RAN), allowing for the exploitation of dense cell infrastructures to construct a perceptive network. In this IEEE Journal on Selected Areas in Communications (JSAC) Special Issue overview, we provide a comprehensive review on the background, range of key applications and state-of-the-art approaches of Integrated Sensing and Communications (ISAC). We commence by discussing the interplay between sensing and communications (S&C) from a historical point of view, and then consider the multiple facets of ISAC and the resulting performance gains. By introducing both ongoing and potential use cases, we shed light on the industrial progress and standardization activities related to ISAC. We analyze a number of performance tradeoffs between S&C, spanning from information theoretical limits to physical layer performance tradeoffs, and the cross-layer design tradeoffs. Next, we discuss the signal processing aspects of ISAC, namely ISAC waveform design and receive signal processing. As a step further, we provide our vision on the deeper integration between S&C within the framework of perceptive networks, where the two functionalities are expected to mutually assist each other, i.e., via communication-assisted sensing and sensing-assisted communications. Finally, we identify the potential integration of ISAC with other emerging communication technologies, and their positive impacts on the future of wireless networks.

The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.

Bacteria are able to maintain a narrow distribution of cell sizes by regulating the timing of cell divisions. In rich nutrient conditions, cells divide much faster than their chromosomes replicate. This implies that cells maintain multiple rounds of chromosome replication per cell division by regulating the timing of chromosome replications. Here, we show that both cell size and chromosome replication may be simultaneously regulated by the long-standing initiator accumulation strategy. The strategy proposes that initiators are produced in proportion to the volume increase and is accumulated at each origin of replication, and chromosome replication is initiated when a critical amount per origin has accumulated. We show that this model maps to the incremental model of size control, which was previously shown to reproduce experimentally observed correlations between various events in the cell cycle and explains the exponential dependence of cell size on the growth rate of the cell. Furthermore, we show that this model also leads to the efficient regulation of the timing of initiation and the number of origins consistent with existing experimental results.

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.