Toll-like Receptor Signaling Rewires Macrophage Metabolism and Promotes Histone Acetylation via ATP-Citrate Lyase.

Toll-like receptor (TLR) activation induces inflammatory responses in macrophages by activating temporally defined transcriptional cascades. Whether concurrent changes in the cellular metabolism that occur upon TLR activation influence the quality of the transcriptional responses remains unknown. Here, we investigated how macrophages adopt their metabolism early after activation to regulate TLR-inducible gene induction.

Charcot-Leyden Crystals Activate the NLRP3 Inflammasome and Cause IL-1β Inflammation in Human Macrophages.

Charcot-Leyden crystals (CLCs) are Galectin-10 protein crystals that can form after eosinophils degranulate. CLCs can appear and persist in tissues from patients with eosinophilic disorders, such as asthma, allergic reactions, and fungal and helminthic infections. Despite abundant reports of their occurrence in human disease, the inflammatory potential of CLCs has remained unknown.

The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation.

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1β.

Genetic alterations of protein-o-mannosyltransferase-1 in glioneuronal and glial brain tumors with subarachnoid spread.

Leptomeningeal spread is a casual but conspicuous finding in both low- and high-grade gliomas. We hypothesized a compromised integrity of the glia limitans-basal lamina complex due to glycosylation defects by loss of protein-o-mannosyltransferase-1 (POMT1) activity, also a well-known feature in developmental brain disorders with leptomeningeal heterotopia. Hypothesizing it as analogous in gliomas, we have performed a comprehensive polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of the POMT1 gene in 41 brain tumor specimens.

Differential Pi3K-pathway activation in cortical tubers and focal cortical dysplasias with balloon cells.

Balloon cells of distinct focal cortical dysplasias type IIb (FCD(IIb)) and giant cells of cortical tubers in tuberous sclerosis (TSC) constitute neuropathological hallmarks and cytological similarities. In TSC, frequent mutations in the TSC1 or TSC2 genes result in mTOR-signaling activity. Here, we addressed whether Pi3K-pathway activation differentiates balloon cells from giant cells.

Activation of Akt independent of PTEN and CTMP tumor-suppressor gene mutations in epilepsy-associated Taylor-type focal cortical dysplasias.

Focal cortical dysplasias (FCD) with Taylor-type balloon cells (FCD(IIb)) are frequently observed in biopsy specimens of patients with pharmacoresistant focal epilepsies. The molecular pathogenesis of FCD(IIb), which lack familial inheritance, is only poorly understood. Due to their highly differentiated, malformative nature and glioneuronal phenotype, FCD(IIb) share neuropathological characteristics with lesions observed in familial disorders such as cortical tubers present in patients with autosomal dominant tuberous sclerosis complex (TSC), related to mutations in the TSC1 or TSC2 genes, and dysplastic gangliocytomas of the cerebellum found in Cowden disease.

Mutational and immunohistochemical analysis of ezrin-, radixin-, moesin (ERM) molecules in epilepsy-associated glioneuronal lesions.

Glioneuronal lesions are frequently observed in biopsy specimens obtained from patients with pharmacoresistant epilepsies, comprising focal cortical dysplasias (FCD) and gangliogliomas. Recent findings point to the phosphoinositide 3-kinase (PI3K) pathway and tuberin/hamartin signaling cascade as being compromised in these lesions. Ezrin, radixin and moesin (ERM-/band-4.