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Aim: To examine the potential of [p16.sup.INK4A] as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep™ smears. Methods: Immunocytochemical analysis of [p16.sup.INK4A] [...]

Examines the potential of P16[sup INK4A] as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections of ThinPrep smears. Cervical glandular intraepithelial neoplasia and cervical intraepithelial neoplasia 1 in cervical biopsies; Analysis of pertinent topics and relevant issues; Implications on clinical pathology.

We introduce bia-binder (BioImage Archive Binder), an open-source, cloud-architectured, and web-based coding environment tailored to bioimage analysis that is freely accessible to all researchers. The service generates easy-to-use Jupyter Notebook coding environments hosted on EMBL-EBI's Embassy Cloud, which provides significant computational resources. The bia-binder architecture is free, open-source and publicly available for deployment. It features fast and direct access to images in the BioImage Archive, the Image Data Resource, and the BioStudies databases. We believe that this service can play a role in mitigating the current inequalities in access to scientific resources across academia. As bia-binder produces permanent links to compiled coding environments, we foresee the service to become widely-used within the community and enable exploratory research. bia-binder is built and deployed using helmsman and helm and released under the MIT licence. It can be accessed at binder.bioimagearchive.org and runs on any standard web browser.

T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection 1 . In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus-the Cortico-Medullary Axis-and used it to perform a spatially resolved analysis. Here, by applying this framework to a curated multimodal single-cell atlas, spatial transcriptomics and high-resolution multiplex imaging data, we demonstrate establishment of the lobular cytokine network, canonical thymocyte trajectories and thymic epithelial cell distributions by the beginning of the the second trimester of fetal development. We pinpoint tissue niches of thymic epithelial cell progenitors and distinct subtypes associated with Hassall's corpuscles and identify divergence in the timing of medullary entry between CD4 and CD8 T cell lineages. These findings provide a basis for a detailed understanding of T lymphocyte development and are complemented with a holistic toolkit for cross-platform imaging data analysis, annotation and OrganAxis construction (TissueTag), which can be applied to any tissue., Competing Interests: Competing interests: J.C.M. has been an employee of Genentech since September 2022. S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, Qiagen, a co-founder and equity holder of TransitionBio and EnsoCell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. The other authors declare no competing interests., (© 2024. The Author(s).)

Bioimage analysis (BIA), a crucial discipline in biological research, overcomes the limitations of subjective analysis in microscopy through the creation and application of quantitative and reproducible methods. The establishment of dedicated BIA support within academic institutions is vital to improving research quality and efficiency and can significantly advance scientific discovery. However, a lack of training resources, limited career paths and insufficient recognition of the contributions made by bioimage analysts prevent the full realization of this potential. This Perspective - the result of the recent The Company of Biologists Workshop 'Effectively Communicating Bioimage Analysis', which aimed to summarize the global BIA landscape, categorize obstacles and offer possible solutions - proposes strategies to bring about a cultural shift towards recognizing the value of BIA by standardizing tools, improving training and encouraging formal credit for contributions. We also advocate for increased funding, standardized practices and enhanced collaboration, and we conclude with a call to action for all stakeholders to join efforts in advancing BIA., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The increasing technical complexity of all aspects involving bioimages, ranging from their acquisition to their analysis, has led to a diversification in the expertise of scientists engaged at the different stages of the discovery process. Although this diversity of profiles comes with the major challenge of establishing fruitful interdisciplinary collaboration, such collaboration also offers a superb opportunity for scientific discovery. In this Perspective, we review the different actors within the bioimaging research universe and identify the primary obstacles that hinder their interactions. We advocate that data sharing, which lies at the heart of innovation, is finally within reach after decades of being viewed as next to impossible in bioimaging. Building on recent community efforts, we propose actions to consolidate the development of a truly interdisciplinary bioimaging culture based on open data exchange and highlight the promising outlook of bioimaging as an example of multidisciplinary scientific endeavour., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

How living systems achieve precision in form and function despite their intrinsic stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these morphomaps revealed that although blastomere divisions desynchronized passively, 8-cell embryos converged toward robust three-dimensional shapes. Using topological analysis and genetic perturbations, we found that embryos progressively changed their cellular connectivity to a preferred topology, which could be predicted by a physical model in which actomyosin contractility and noise facilitate topological transitions, lowering surface energy. This mechanism favored regular embryo packing and promoted a higher number of inner cells in the 16-cell embryo. Synchronized division reduced embryo packing and generated substantially more misallocated cells and fewer inner-cell-mass cells. These findings suggest that stochasticity in division timing contributes to robust patterning.

Images are at the core of most modern biological experiments and are used as a major source of quantitative information. Numerous algorithms are available to process images and make them more amenable to be measured. Yet the nature of the quantitative output that is useful for a given biological experiment is uniquely dependent upon the question being investigated. Here, we discuss the 3 main types of information that can be extracted from microscopy data: intensity, morphology, and object counts or categorical labels. For each, we describe where they come from, how they can be measured, and what may affect the relevance of these measurements in downstream data analysis. Acknowledging that what makes a measurement 'good' is ultimately down to the biological question being investigated, this review aims at providing readers with a toolkit to challenge how they quantify their own data and be critical of conclusions drawn from quantitative bioimage analysis experiments., (© 2023 European Molecular Biology Laboratory (EMBL) and The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.)

Motivation: The nuclear pore complex (NPC) is the only passageway for macromolecules between nucleus and cytoplasm, and an important reference standard in microscopy: it is massive and stereotypically arranged. The average architecture of NPC proteins has been resolved with pseudoatomic precision, however observed NPC heterogeneities evidence a high degree of divergence from this average. Single-molecule localization microscopy (SMLM) images NPCs at protein-level resolution, whereupon image analysis software studies NPC variability. However, the true picture of this variability is unknown. In quantitative image analysis experiments, it is thus difficult to distinguish intrinsically high SMLM noise from variability of the underlying structure., Results: We introduce CIR4MICS ('ceramics', Configurable, Irregular Rings FOR MICroscopy Simulations), a pipeline that synthesizes ground truth datasets of structurally variable NPCs based on architectural models of the true NPC. Users can select one or more N- or C-terminally tagged NPC proteins, and simulate a wide range of geometric variations. We also represent the NPC as a spring-model such that arbitrary deforming forces, of user-defined magnitudes, simulate irregularly shaped variations. Further, we provide annotated reference datasets of simulated human NPCs, which facilitate a side-by-side comparison with real data. To demonstrate, we synthetically replicate a geometric analysis of real NPC radii and reveal that a range of simulated variability parameters can lead to observed results. Our simulator is therefore valuable to test the capabilities of image analysis methods, as well as to inform experimentalists about the requirements of hypothesis-driven imaging studies., Availability and Implementation: Code: https://github.com/uhlmanngroup/cir4mics. Simulated data: BioStudies S-BSST1058., (© The Author(s) 2023. Published by Oxford University Press.)

Embryo implantation into the uterus marks a key transition in mammalian development. In mice, implantation is mediated by the trophoblast and is accompanied by a morphological transition from the blastocyst to the egg cylinder. However, the roles of trophoblast-uterine interactions in embryo morphogenesis during implantation are poorly understood due to inaccessibility in utero and the remaining challenges to recapitulate it ex vivo from the blastocyst. Here, we engineer a uterus-like microenvironment to recapitulate peri-implantation development of the whole mouse embryo ex vivo and reveal essential roles of the physical embryo-uterine interaction. We demonstrate that adhesion between the trophoblast and the uterine matrix is required for in utero-like transition of the blastocyst to the egg cylinder. Modeling the implanting embryo as a wetting droplet links embryo shape dynamics to the underlying changes in trophoblast adhesion and suggests that the adhesion-mediated tension release facilitates egg cylinder formation. Light-sheet live imaging and the experimental control of the engineered uterine geometry and trophoblast velocity uncovers the coordination between trophoblast motility and embryo growth, where the trophoblast delineates space for embryo morphogenesis., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Technological advancements in biology and microscopy have empowered a transition from bioimaging as an observational method to a quantitative one. However, as biologists are adopting quantitative bioimaging and these experiments become more complex, researchers need additional expertise to carry out this work in a rigorous and reproducible manner. This Essay provides a navigational guide for experimental biologists to aid understanding of quantitative bioimaging from sample preparation through to image acquisition, image analysis, and data interpretation. We discuss the interconnectedness of these steps, and for each, we provide general recommendations, key questions to consider, and links to high-quality open-access resources for further learning. This synthesis of information will empower biologists to plan and execute rigorous quantitative bioimaging experiments efficiently., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Senft et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Electron microscopy (EM) provides a uniquely detailed view of cellular morphology, including organelles and fine subcellular ultrastructure. While the acquisition and (semi-)automatic segmentation of multicellular EM volumes are now becoming routine, large-scale analysis remains severely limited by the lack of generally applicable pipelines for automatic extraction of comprehensive morphological descriptors. Here, we present a novel unsupervised method for learning cellular morphology features directly from 3D EM data: a neural network delivers a representation of cells by shape and ultrastructure. Applied to the full volume of an entire three-segmented worm of the annelid Platynereis dumerilii , it yields a visually consistent grouping of cells supported by specific gene expression profiles. Integration of features across spatial neighbours can retrieve tissues and organs, revealing, for example, a detailed organisation of the animal foregut. We envision that the unbiased nature of the proposed morphological descriptors will enable rapid exploration of very different biological questions in large EM volumes, greatly increasing the impact of these invaluable, but costly resources., Competing Interests: VZ, JH, VU, DA, AK No competing interests declared, (© 2023, Zinchenko, Hugger et al.)

Motivation: Rotated template matching is an efficient and versatile algorithm to analyze microscopy images, as it automates the detection of stereotypical structures, such as organelles that can appear at any orientation. Its performance however quickly degrades in noisy image data., Results: We introduce Steer'n'Detect, an ImageJ plugin implementing a recently published algorithm to detect patterns of interest at any orientation with high accuracy from a single template in 2D images. Steer'n'Detect provides a faster and more robust substitute to template matching. By adapting to the statistics of the image background, it guarantees accurate results even in the presence of noise. The plugin comes with an intuitive user interface facilitating results analysis and further post-processing., Availability and Implementation: https://github.com/Biomedical-Imaging-Group/Steer-n-Detect., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)