Glioblastoma is the most common and aggressive primary brain cancer. Recent isolation and characterization of brain tumor-initiating cells supports the concept that transformed neural stem cells may seed glioblastoma. We previously identified a wide array of mesenchymal tissue transcripts overexpressed in a broad set of primary glioblastoma (de novo) tumors but not in secondary glioblastoma (derived from lower-grade) tumors, low-grade astrocytomas, or normal brain tissues. Here, we extend this observation and show that a subset of primary glioblastoma tumors and their derived tumor lines express cellular and molecular markers that are associated with mesenchymal stem cells (MSC) and that glioblastoma cell cultures can be induced to differentiate into multiple mesenchymal lineage-like cell types. These findings suggest either that a subset of primary glioblastomas derive from transformed stem cells containing MSC-like properties and retain partial phenotypic aspects of a MSC nature in tumors or that glioblastomas activate a series of genes that result in mesenchymal properties of the cancer cells to effect sustained tumor growth and malignant progression. (Mol Cancer Res 2006;4(9):607 -19)

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-009-9919-z) contains supplementary material, which is available to authorized users.

Compared with carbon nanotubes and graphene, graphene oxide (GO) exhibits excellent water solubility and biocompatibility in addition to the characteristic G band in Raman spectra. Therefore GO might be able to act as a flexible Raman probe to image cells or tissues through Raman mapping. However, the weak intensity of the G band restricts such applications of GO. Here we decorated GO with Au nanoparticles and found that the Raman intensity of GO in aqueous dispersions were remarkably enhanced by the surface enhancement effect. Therefore, rapid Raman imaging for Hela 229 cells was realized using Au/GO hybrids as Raman probes. The cell internalization mechanism of GO and Au/GO hybrids were also studied using Raman imaging. An endocytosis pathway was proposed from the results. In addition, the aqueous dispersions of Au/GO hybrids are stable for several weeks. Therefore, relying on the surface enhancement effect of Au nanoparticles, GO exhibits great potential as a general Raman imaging tool for biosystems.

Verticillium wilt in cotton caused by Verticillium dahliae is one of the most serious plant diseases worldwide. Because no known fungicides or cotton cultivars provide sufficient protection against this pathogen, V. dahliae causes major crop yield losses. Here, an isolated cotton endophytic bacterium, designated Bacillus amyloliquefaciens 41B-1, exhibited greater than 50% biocontrol efficacy against V. dahliae in cotton plants under greenhouse conditions. Through high-performance liquid chromatography and mass analysis of the filtrate, we found that the antifungal compounds present in the strain 41B-1 culture filtrate were a series of isoforms of iturins. The purified iturins suppressed V. dahliae microsclerotial germination in the absence or presence of cotton. Treatment with the iturins induced reactive oxygen species bursts, Hog1 mitogen-activated protein kinase (MAPK) activation and defects in cell wall integrity. The oxidative stress response and high-osmolarity glycerol pathway contribute to iturins resistance in V. dahliae. In contrast, the Slt2 MAPK pathway may be involved in iturins sensitivity in this fungus. In addition to antagonism, iturins could induce plant defence responses as activators and mediate pathogen-associated molecular pattern-triggered immunity. These findings suggest that iturins may affect fungal signalling pathways and mediate plant defence responses against V. dahliae.

Modulating germ cell death and survival have significant therapeutic potential for male infertility and contraception. We have shown previously that IGF binding protein 3 (IGFBP3) gene expression is up-regulated in human testis when germ cell apoptosis is induced by intratesticular hormonal deprivation created by testosterone administration. Humanin (HN) is a binding partner of IGFBP3, and both are expressed in rat testes. We therefore hypothesized that IGFBP3, a proapoptotic factor, and HN, an antiapoptotic factor, are important regulators of male germ cell apoptosis. Whereas baseline apoptosis in the testis was equivalent between Igfbp3 knockout and wild-type mice, treatment with GnRH antagonist (GnRH-A) for 2 wk induced germ cell apoptosis in wild type, which was dramatically reduced in Igfbp3 knockout mice. To investigate the direct effects of IGFBP3 and HN on germ cell apoptosis, intratesticular administration of IGFBP3 for 5 d in rats induced a 4.2- and 3.8-fold increase in apoptosis at stages VII-VIII and XIV-I of the seminiferous epithelium cycle, respectively. GnRH-A treatment for 5 d increased apoptosis, mainly at stages VII-VIII. Addition of IGFBP3 to GnRH-A treatment enhanced apoptosis to 39.3-fold at stages VII-VIII, which was higher than either treatment alone. Intratesticular injection of HN significantly decreased GnRH-A-induced apoptosis at stages XIV-I but not stages VII-VIII. We conclude that IGFBP3 and HN play key roles in the coordinated regulation of testicular germ cell homeostasis. Perturbation of this interaction is important in enhancing or preventing germ cell death, providing new targets for future therapies.

Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury and behavioral deficits. Pericytes influence blood-brain barrier (BBB) integrity and cerebral blood flow. Under hypoxic conditions, pericytes detach from perivascular locations increasing vessel permeability and neuronal injury. This study characterizes the time course of BBB dysfunction and pericyte coverage following murine experimental CCH secondary to bilateral carotid artery stenosis (BCAS). Mice underwent BCAS or sham operation. On post-procedure days 1, 3, 7 and 30, corpus callosum BBB permeability was characterized using Evans blue (EB) extravasation and IgG staining and pericyte coverage/count was calculated. The BCAS cohort demonstrated increased EB extravasation on postoperative days 1 ( p = 0.003) 3 ( p = 0.002), and 7 ( p = 0.001) when compared to sham mice. Further, EB extravasation was significantly greater ( p = 0.05) at day 3 than at day 30 in BCAS mice. BCAS mice demonstrated a nadir in pericyte coverage and count on post-operative day 3 ( p < 0.05, compared to day 7, day 30 and sham). Decreased pericyte coverage/count and increased BBB permeability are most pronounced on postoperative day 3 following murine CCH. This precedes any notable WM injury or behavioral deficits.

The purpose of this review is to describe recent clinical and epidemiological studies examining the adverse effects of urban air pollution on the central nervous system (CNS). Air pollution and particulate matter (PM) are associated with neuroinflammation and reactive oxygen species (ROS). These processes affect multiple CNS pathways. The conceptual framework of this review focuses on adverse effects of air pollution with respect to neurocognition, white matter disease, stroke, and carotid artery disease. Both children and older individuals exposed to air pollution exhibit signs of cognitive dysfunction. However, evidence on middle-aged cohorts is lacking. White matter injury secondary to air pollution exposure is a putative mechanism for neurocognitive decline. Air pollution is associated with exacerbations of neurodegenerative conditions such as Alzheimer’s and Parkinson’s Diseases. Increases in stroke incidences and mortalities are seen in the setting of air pollution exposure and CNS pathology is robust. Large populations living in highly polluted environments are at risk. This review aims to outline current knowledge of air pollution exposure effects on neurological health.

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