Modality Attention and Sampling Enables Deep Learning with Heterogeneous Marker Combinations in Fluorescence Microscopy

Fluorescence microscopy allows for a detailed inspection of cells, cellular networks, and anatomical landmarks by staining with a variety of carefully-selected markers visualized as color channels. Quantitative characterization of structures in acquired images often relies on automatic image analysis methods. Despite the success of deep learning methods in other vision applications, their potential for fluorescence image analysis remains underexploited. One reason lies in the considerable workload required to train accurate models, which are normally specific for a given combination of markers, and therefore applicable to a very restricted number of experimental settings. We herein propose Marker Sampling and Excite, a neural network approach with a modality sampling strategy and a novel attention module that together enable ($i$) flexible training with heterogeneous datasets with combinations of markers and ($ii$) successful utility of learned models on arbitrary subsets of markers prospectively. We show that our single neural network solution performs comparably to an upper bound scenario where an ensemble of many networks is na\"ively trained for each possible marker combination separately. In addition, we demonstrate the feasibility of our framework in high-throughput biological analysis by revising a recent quantitative characterization of bone marrow vasculature in 3D confocal microscopy datasets. Not only can our work substantially ameliorate the use of deep learning in fluorescence microscopy analysis, but it can also be utilized in other fields with incomplete data acquisitions and missing modalities.Comment: 17 pages, 5 figures, 3 pages supplement (3 figures

Chronic viral infections persistently alter marrow stroma and impair hematopoietic stem cell fitness

Chronic viral infections are associated with hematopoietic suppression, bone marrow (BM) failure, and hematopoietic stem cell (HSC) exhaustion. However, how persistent viral challenge and inflammatory responses target BM tissues and perturb hematopoietic competence remains poorly understood. Here, we combine functional analyses with advanced 3D microscopy to demonstrate that chronic infection with lymphocytic choriomeningitis virus leads to (1) long-lasting decimation of the BM stromal network of mesenchymal CXCL12-abundant reticular cells, (2) proinflammatory transcriptional remodeling of remaining components of this key niche subset, and (3) durable functional defects and decreased competitive fitness in HSCs. Mechanistically, BM immunopathology is elicited by virus-specific, activated CD8 T cells, which accumulate in the BM via interferon-dependent mechanisms. Combined antibody-mediated inhibition of type I and II IFN pathways completely preempts degeneration of CARc and protects HSCs from chronic dysfunction. Hence, viral infections and ensuing immune reactions durably impact BM homeostasis by persistently decreasing the competitive fitness of HSCs and disrupting essential stromal-derived, hematopoietic-supporting cues

How Policies That Impact Migrants Amplify or Mitigate Stigma Process

How are stigma processes refl ected in policies that impact migrants? How might policies that impact migrants amplify and/or mitigate stigma processes for migrants? This chapter explores the role of policy narratives and frameworks (e.g., assimilation, integration, multiculturalism) in shaping specifi c policy types (e.g., targeted, universal, mainstream) that diff erentially conceptualize and aff ect the roles, rights, and opportunities of migrants in society. The complexity of the policy-making process is examined, including the specifi c policy context and political discourse, trade-off s leading to a mix of policy types, competing policies across jurisdictions (e.g., international, federal, regional), and diff erential implementation of policies. Throughout, policies are considered that can intentionally or unintentionally generate, amplify, and/or mitigate stigma processes. In addition, this chapter examines consequences of these policy-generated stigma experiences for both migrants and nonmigrants, the feedback processes from these stigma experiences to the demand for policy change, and strategies to improve policy making with specifi c consideration for stigma in the context of migration-generated diversity. Empirical gaps in the literature are noted and recommendations are made to address these knowledge gaps

Imaging and spatial analysis of hematopoietic stem cell niches

Hematopoietic stem cells (HSCs) have been long proposed to reside in defined anatomical locations within bone marrow (BM) tissues in direct contact or close proximity to nurturing cell types. Imaging techniques that allow the simultaneous mapping of HSCs and interacting cell types have been central to the discovery of basic principles of these so-called HSC niches. Despite major progress in the field, a quantitative and comprehensive model of the cellular and molecular components that define these specialized microenvironments is lacking to date, and uncertainties remain on the preferential localization of HSCs in the context of complex BM tissue landscapes. Recent technological breakthroughs currently allow for the quantitative spatial analysis of BM cellular components with extraordinary precision. Here, we critically discuss essential technical aspects related to imaging approaches, image processing tools, and spatial statistics, which constitute the three basic elements of rigorous quantitative spatial analyses of HSC niches in the BM microenvironment

Cultural mapping 4.0 : participatory regional cultural planning in theory and practice

Cultural mapping aims to capture and visualize tangible and intangible cultural assets. This extended abstract proposes the consequent extension of analogue forms of cultural mapping using digital technologies, and its contribution is two-fold. First, the necessary theoretical basis is provided by a literature review of the still-young field of cultural mapping and the complementary disciplines of participatory mapping and digital storymapping. Second, we propose a digitally enhanced Cultural Mapping 4.0 vision based on a case study from an ongoing research project in the Lake Constance region. Digital participatory mapping approaches are applied to capture data, and to validate and disseminate the results, story-mapping a spatial form of digital storytelling is used

Global Transcriptomic Profiling of the Bone Marrow Stromal Microenvironment during Postnatal Development, Aging, and Inflammation

Bone marrow (BM) stromal cells provide the regulatory framework for hematopoiesis and contribute to developmental stage-specific niches, such as those preserving hematopoietic stem cells. Despite advances in our understanding of stromal function, little is known about the transcriptional changes that this compartment undergoes throughout lifespan and during adaptation to stress. Using RNA sequencing, we perform transcriptional analyses of four principal stromal subsets, namely CXCL12-abundant reticular, platelet-derived growth factor receptor (PDGFR)-α$^{+}$Sca1$^{+}$, sinusoidal, and arterial endothelial cells, from early postnatal, adult, and aged mice. Our data reveal (1) molecular fingerprints defining cell-specific anatomical and functional features, (2) a radical reprogramming of pro-hematopoietic, immune, and matrisomic transcriptional programs during the transition from juvenile stages to adulthood, and (3) the aging-driven progressive upregulation of pro-inflammatory gene expression in stroma. We further demonstrate that transcriptomic pathways elicited in vivo by prototypic microbial molecules are largely recapitulated during aging, thereby supporting the inflammatory basis of age-related adaptations of BM hematopoietic function

Cultural Mapping 4.0

Cultural mapping aims to capture and visualize tangible and intangible cultural assets. This extend abstract proposes the consequent extension of analogue forms of cultural mapping using digital technologies, and its contribution is two-fold. First, the necessary theoretical basis is provided by a literature review of the still-young field of cultural mapping and the complementary disciplines of participatory mapping and digital story-mapping. Second, we propose a digitally enhanced Cultural Mapping 4.0 vision based on a case study from an ongoing research project in the Lake Constance region. Digital participatory mapping approaches are applied to capture data, and to validate and disseminate the results, story-mapping - a spatial form of digital storytelling - is used