CD45 and CD148 Are Critically Involved in Neutrophil Recruitment and Function During Inflammatory Arthritis in Mice.

Neutrophils play a key role in autoimmune diseases like rheumatoid arthritis, contributing to tissue damage through rapid recruitment and activation. In this study, we investigated the regulatory properties of two receptor-like tyrosine phosphatases (RPTPs), CD45 and CD148, in inflammatory arthritis. Using an in vivo mouse model of K/BxN serum transfer-induced arthritis, we found that CD45 and CD148 feature distinct regulatory properties during inflammatory arthritis.

ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.

Embryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations - RG-like, NProg-like and NB-like - positioned within a putative neurodevelopmental hierarchy.

RhoA GAP Myo9b regulates β2-integrin activity and neutrophil recruitment during murine acute kidney injury.

An acute inflammatory response to infection or sterile injury involves an adequate activation and recruitment of leukocytes. Activation of β2-integrins is required for neutrophil recruitment and is also mandatory for various neutrophil cell-intrinsic functions. Guanosine triphosphatases (GTPases) are key regulators of the actin cytoskeleton and are required for β2-integrin activation.

Multiomic analysis uncovers a continuous spectrum of differentiation and Wnt-MDK-driven immune evasion in hepatoblastoma.

Background & Aims: Hepatoblastoma is the most common pediatric cancer of the liver, with the majority of cases displaying activating mutations in the Wnt/β-catenin pathway. Understanding the complex milieu of the tumor microenvironment has resulted in promising new therapies for adult cancers, but similar approaches in pediatric cancers are still lacking. We aimed to provide a comprehensive analysis of the tumor microenvironment of hepatoblastoma, unveiling its spatial architecture and key signaling mechanisms.

msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysis.

Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data.

β-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus.

Disease tolerance is an evolutionarily conserved host defense strategy that preserves tissue integrity and physiology without affecting pathogen load. Unlike host resistance, the mechanisms underlying disease tolerance remain poorly understood. In the present study, we investigated whether an adjuvant (β-glucan) can reprogram innate immunity to provide protection against influenza A virus (IAV) infection.

Proteomic Characterization of 1000 Human and Murine Neutrophils Freshly Isolated From Blood and Sites of Sterile Inflammation.

Neutrophils are indispensable for defense against pathogens. Injured tissue-infiltrated neutrophils can establish a niche of chronic inflammation and promote degeneration. Studies investigated transcriptome of single-infiltrated neutrophils which could misinterpret molecular states of these post mitotic cells.

Neural dynamic foundations of a theory of higher cognition: the case of grounding nested phrases.

Because cognitive competences emerge in evolution and development from the sensory-motor domain, we seek a neural process account for higher cognition in which all representations are necessarily grounded in perception and action. The challenge is to understand how hallmarks of higher cognition, productivity, systematicity, and compositionality, may emerge from such a bottom-up approach. To address this challenge, we present key ideas from Dynamic Field Theory which postulates that neural populations are organized by recurrent connectivity to create stable localist representations.

Gasdermin D drives focal crystalline thrombotic microangiopathy by accelerating immunothrombosis and necroinflammation.

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein that serves as the final downstream effector of the pyroptosis/interleukin-1β (IL-1β) pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd deficiency ameliorated immunothrombosis, acute tissue injury, and failure.

A Neural Dynamic Model of the Perceptual Grounding of Spatial and Movement Relations.

How does the human brain link relational concepts to perceptual experience? For example, a speaker may say "the cup to the left of the computer" to direct the listener's attention to one of two cups on a desk. We provide a neural dynamic account for both perceptual grounding, in which relational concepts enable the attentional selection of objects in the visual array, and for the generation of descriptions of the visual array using relational concepts. In the model, activation in neural populations evolves dynamically under the influence of both inputs and strong interaction as formalized in dynamic field theory.

Treatment with the calcineurin inhibitor and immunosuppressant cyclosporine A impairs sensorimotor gating in Dark Agouti rats.

Rationale: Calcineurin is a protein regulating cytokine expression in T lymphocytes and calcineurin inhibitors such as cyclosporine A (CsA) are widely used for immunosuppressive therapy. It also plays a functional role in distinct neuronal processes in the central nervous system. Disturbed information processing as seen in neuropsychiatric disorders is reflected by deficient sensorimotor gating, assessed as prepulse inhibition (PPI) of the acoustic startle response (ASR).

Neutrophil dynamics, plasticity and function in acute neurodegeneration following neonatal hypoxia-ischemia.

Neonatal encephalopathy following hypoxia-ischemia (HI) is a major cause of long-term morbidity and mortality in children. Even though HI-induced neuroinflammation, involving infiltration of peripheral immune cells into the CNS has been associated with disease pathogenesis, the specific role of neutrophils is highly debated. Due to immaturity of the neonatal immune system, it has been assumed that neutrophils are less clinically relevant in neonatal HI-induced brain injury.

A Neural Dynamic Model Generates Descriptions of Object-Oriented Actions.

Describing actions entails that relations between objects are discovered. A pervasively neural account of this process requires that fundamental problems are solved: the neural pointer problem, the binding problem, and the problem of generating discrete processing steps from time-continuous neural processes. We present a prototypical solution to these problems in a neural dynamic model that comprises dynamic neural fields holding representations close to sensorimotor surfaces as well as dynamic neural nodes holding discrete, language-like representations.

Developing Dynamic Field Theory Architectures for Embodied Cognitive Systems with .

Embodied artificial cognitive systems, such as autonomous robots or intelligent observers, connect cognitive processes to sensory and effector systems in real time. Prime candidates for such embodied intelligence are neurally inspired architectures. While components such as forward neural networks are well established, designing pervasively autonomous neural architectures remains a challenge.