Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.

The sub-ventricular zone (SVZ) is the most well-characterized neurogenic area in the mammalian brain. We previously showed that in 65% of patients with glioblastoma (GBM), the SVZ is a reservoir of cancer stem-like cells that contribute to treatment resistance and emergence of recurrence. Here, we built a single-nucleus RNA-sequencing-based microenvironment landscape of the tumor mass (T_Mass) and the SVZ (T_SVZ) of 15 GBM patients and 2 histologically normal SVZ (N_SVZ) samples as controls. We identified a mesenchymal signature in the T_SVZ of GBM patients: tumor cells from the T_SVZ relied on the ZEB1 regulatory network, whereas tumor cells in the T_Mass relied on the TEAD1 regulatory network. Moreover, the T_SVZ microenvironment was predominantly characterized by tumor-supportive microglia, which spatially co-exist and establish heterotypic interactions with tumor cells. Lastly, differential gene expression analyses, predictions of ligand-receptor and incoming/outgoing interactions, and functional assays revealed that the IL-1ß/IL-1RAcP and Wnt-5a/Frizzled-3 pathways are therapeutic targets in the T_SVZ microenvironment. Our data provide insights into the biology of the SVZ in GBM patients and identify specific targets of this microenvironment.

Diagnosis of ventriculoperitoneal shunt infection using [F-18]-FDG PET: a case report.

Infection of cerebrospinal fluid (CSF) shunts is a common occurrence and can often be difficult to diagnose using standard analysis of shunt fluid. This article presents the first case report on the diagnosis of a CSF shunt infection on FDG PET scan. A 26-year-old female underwent ventriculoperitoneal shunt placement after developing a pseudomeningocele subsequent to a suboccipital craniectomy for Chiari malformation. Two months later, the patient presented with abdominal pain and non-specific symptoms and was found to have a perisplenic abscess for which she was adequately treated. Failure of her symptoms to solve and an initial negative shunt CSF analysis prompted the search for other sources of infection. An FDG PET scan performed a week later found evidence of increase tracer uptake around the distal tip of the catheter and a repeat shunt CSF analysis showed evidence of CSF infection. FDG PET may be useful in diagnosing shunt related infections in case of high clinical suspicion when standard diagnostic modalities fail to diagnose hardware infection.

Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau.

Alzheimer's disease-like neurofibrillary pathology is neither seen in rodents nor in transgenic animals expressing the disease causing mutant human APP or mutant human presenilins. Whether the absence of this pathology is due to inability of the murine tau to self assemble into filaments or due to some other factors is not understood. In this study, we compared recombinant murine and human taus in their ability to form filaments by AD-like hyperphosphorylation in vitro. Human and murine taus, 0N4R, were generated as recombinant proteins and phosphorylated with rat brain extract as a source of protein kinases. We found that murine tau could be hyperphosphorylated to similar stoichiometry and manner as human tau. Upon hyperphosphorylation, murine tau was able to self polymerize into bundles of paired helical filament- and straight filament-like morphology. The filaments obtained from self assembly of murine tau closely resembled those formed from identically treated human tau. Moreover, like human tau, 60-70% of murine tau aggregated on hyperphosphorylation.