TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothelial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery.

Bone metabolism in complex regional pain syndrome.

Introduction: Patients with complex regional pain syndrome (CRPS) often show disturbed bone metabolism, assessed using three-phase bone scintigraphy (TPBS). However, current methods lack automation and standardisation. Bone serum markers have been proposed as biomarkers, but their utility is unclear.

The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking.

Neuroimmune interactions play a significant role in regulating synaptic plasticity in both the healthy and diseased brain. The complement pathway, an extracellular proteolytic cascade, exemplifies these interactions. Its activation triggers microglia-dependent synaptic elimination via the complement receptor 3 (CR3).

An unusual case of Brodie's abscess in the humerus of an adult female.

Brodie's abscess is a manifestation of subacute to chronic osteomyelitis, characterized as intraosseous abscess formation, usually on the metaphysis of the long tubular bones in the lower extremities of male pediatric patients. Clinically, Brodie's abscess presents with atraumatic bone pain of an insidious onset, with absence of systemic findings. Delay in diagnosis is common, as diagnostic imaging, followed by biopsy for culture and histologic examination are generally required to secure a diagnosis of Brodie's abscess.

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.

Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation - a prevalent locus of brain disease etiology - in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 () gene. We found that overexpression of mouse () in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex.

Setting the geological scene for the origin of life and continuing open questions about its emergence.

The origin of life is one of the most fundamental questions of humanity. It has been and is still being addressed by a wide range of researchers from different fields, with different approaches and ideas as to how it came about. What is still incomplete is constrained information about the environment and the conditions reigning on the Hadean Earth, particularly on the inorganic ingredients available, and the stability and longevity of the various environments suggested as locations for the emergence of life, as well as on the kinetics and rates of the prebiotic steps leading to life.

Development and Evaluation of an MRI Artifact-Free Aneurysm Clip.

Background And Objectives: The digital subtraction angiography is still the gold standard in the follow-up after aneurysm surgery, although it remains a repeating invasive technique with accumulating X-ray exposure. An alternative magnetic resonance angiography has the disadvantage of metal-related artifacts. A metal-free aneurysm clip could overcome this problem.

C4 induces pathological synaptic loss by impairing AMPAR trafficking.

During development, activation of the complement pathway, an extracellular proteolytic cascade, results in microglia-dependent synaptic elimination via complement receptor 3 (CR3). Here, we report that decreased connectivity caused by overexpression of (C4-OE), a schizophrenia-associated gene, is CR3 independent. Instead, C4-OE triggers GluR1 degradation through an intracellular mechanism involving endosomal trafficking protein SNX27, resulting in pathological synaptic loss.

A pipeline for STED super-resolution imaging and Imaris analysis of nanoscale synapse organization in mouse cortical brain slices.

Advances in super-resolution imaging enable us to delve into its intricate structural and functional complexities with unprecedented detail. Here, we present a pipeline to visualize and analyze the nanoscale organization of cortical layer 1 apical dendritic spines in the mouse prefrontal cortex. We describe steps for brain slice preparation, immunostaining, stimulated emission depletion super-resolution microscopy, and data analysis using the Imaris software package.

Myelin barrier breakdown, mechanical hypersensitivity, and painfulness in polyneuropathy with claudin-12 deficiency.

Background: The blood-nerve and myelin barrier shield peripheral neurons and their axons. These barriers are sealed by tight junction proteins, which control the passage of potentially noxious molecules including proinflammatory cytokines via paracellular pathways. Peripheral nerve barrier breakdown occurs in various neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and traumatic neuropathy.

Heterogeneous levels of delta-like 4 within a multinucleated niche cell maintains muscle stem cell diversity.

The quiescent muscle stem cell (QSC) pool is heterogeneous and generally characterized by the presence and levels of intrinsic myogenic transcription factors. Whether extrinsic factors maintain the diversity of states across the QSC pool remains unknown. The muscle fiber is a multinucleated syncytium that serves as a niche to QSCs, raising the possibility that the muscle fiber regulates the diversity of states across the QSC pool.

Molecular and clinical markers of pain relief in complex regional pain syndrome: An observational study.

Background: Complex regional pain syndrome (CRPS) is marked by disproportionate pain after trauma. Whilst the long-term outcome is crucial to patients, predictors or biomarkers of the course of pain or CRPS symptoms are still lacking. In particular, microRNAs, such as miR-223, decreased in CRPS, have been described only in cross-sectional studies.

Highly unstable heterogeneous representations in VIP interneurons of the anterior cingulate cortex.

A hallmark of the anterior cingulate cortex (ACC) is its functional heterogeneity. Functional and imaging studies revealed its importance in the encoding of anxiety-related and social stimuli, but it is unknown how microcircuits within the ACC encode these distinct stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to modulate the activity of pyramidal cells in local microcircuits, but it is unknown whether VIP cells in the ACC (VIP) are engaged by particular contexts or stimuli.

Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy.

Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN.

Pain Control by Targeting Oxidized Phospholipids: Functions, Mechanisms, Perspectives.

Within the lipidome oxidized phospholipids (OxPL) form a class of chemically highly reactive metabolites. OxPL are acutely produced in inflamed tissue and act as endogenous, proalgesic (pain-inducing) metabolites. They excite sensory, nociceptive neurons by activating transient receptor potential ion channels, specifically TRPA1 and TRPV1.

COVID-19 Induced Acute Respiratory Distress Syndrome-A Multicenter Observational Study.

Proportions of patients dying from the coronavirus disease-19 (COVID-19) vary between different countries. We report the characteristics; clinical course and outcome of patients requiring intensive care due to COVID-19 induced acute respiratory distress syndrome (ARDS). This is a retrospective, observational multicentre study in five German secondary or tertiary care hospitals.

Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin.

Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events leading to cell fate commitment. Here we developed simultaneous high-throughput ATAC and RNA expression with sequencing (SHARE-seq), a highly scalable approach for measurement of chromatin accessibility and gene expression in the same single cell, applicable to different tissues.

Stabilization of Delphinidin in Complex with Sulfobutylether-β-Cyclodextrin Allows for Antinociception in Inflammatory Pain.

Delphinidin (DEL) is a plant-derived antioxidant with clinical potential to treat inflammatory pain but suffers from poor solubility and low bioavailability. The aim of the study was to develop a well-tolerated cyclodextrin (CD)-DEL complex with enhanced bioavailability and to investigate the mechanisms behind its antinociceptive effects in a preclinical model of inflammatory pain. CD-DEL was highly soluble and stable in aqueous solution, and was nontoxic.

Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma.

Regulatory networks that maintain functional, differentiated cell states are often dysregulated in tumor development. Here, we use single-cell epigenomics to profile chromatin state transitions in a mouse model of lung adenocarcinoma (LUAD). We identify an epigenomic continuum representing loss of cellular identity and progression toward a metastatic state.

Functionally heterogeneous human satellite cells identified by single cell RNA sequencing.

Although heterogeneity is recognized within the murine satellite cell pool, a comprehensive understanding of distinct subpopulations and their functional relevance in human satellite cells is lacking. We used a combination of single cell RNA sequencing and flow cytometry to identify, distinguish, and physically separate novel subpopulations of human PAX7+ satellite cells (Hu-MuSCs) from normal muscles. We found that, although relatively homogeneous compared to activated satellite cells and committed progenitors, the Hu-MuSC pool contains clusters of transcriptionally distinct cells with consistency across human individuals.

Aging induces aberrant state transition kinetics in murine muscle stem cells.

Murine muscle stem cells (MuSCs) experience a transition from quiescence to activation that is required for regeneration, but it remains unknown if the trajectory and dynamics of activation change with age. Here, we use time-lapse imaging and single cell RNA-seq to measure activation trajectories and rates in young and aged MuSCs. We find that the activation trajectory is conserved in aged cells, and we develop effective machine-learning classifiers for cell age.

Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells.

Satellite cells (SCs) reside in a dormant state during tissue homeostasis. The specific paracrine agents and niche cells that maintain SC quiescence remain unknown. We find that Wnt4 produced by the muscle fiber maintains SC quiescence through RhoA.