CDC20 regulates sensitivity to chemotherapy and radiation in glioblastoma stem cells

Glioblastoma stem cells (GSCs) are an important subpopulation in glioblastoma, implicated in tumor growth, tumor recurrence, and radiation resistance. Understanding the cellular mechanisms for chemo- and radiation resistance could lead to the development of new therapeutic strategies. Here, we demonstrate that CDC20 promotes resistance to chemotherapy and radiation therapy. CDC20 knockdown does not increase TMZ- and radiation-induced DNA damage, or alter DNA damage repair, but rather promotes cell death through accumulation of the pro-apoptotic protein, Bim. Our results identify a CDC20 signaling pathway that regulates chemo- and radiosensitivity in GSCs, with the potential for CDC20-targeted therapeutic strategies in the treatment of glioblastoma

Competitive binding of E3 ligases TRIM26 and WWP2 controls SOX2 in glioblastoma

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance

A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells

SummaryGlioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma

Using magnetic resonance imaging to assess visual deficits : a review

PURPOSE: Over the last two decades, magnetic resonance imaging (MRI) has been widely used in neuroscience research to assess both structure and function in the brain in health and disease. With regard to vision research, prior to the advent of MRI, researchers relied on animal physiology and human post-mortem work to assess the impact of eye disease on visual cortex and connecting structures. Using MRI, researchers can non-invasively examine the effects of eye disease on the whole visual pathway, including the lateral geniculate nucleus, striate and extrastriate cortex. This review aims to summarise research using MRI to investigate structural, chemical and functional effects of eye diseases, including: macular degeneration, retinitis pigmentosa, glaucoma, albinism, and amblyopia. RECENT FINDINGS: Structural MRI has demonstrated significant abnormalities within both grey and white matter densities across both visual and non-visual areas. Functional MRI studies have also provided extensive evidence of functional changes throughout the whole of the visual pathway following visual loss, particularly in amblyopia. MR spectroscopy techniques have also revealed several abnormalities in metabolite concentrations in both glaucoma and age-related macular degeneration. GABA-edited MR spectroscopy on the other hand has identified possible evidence of plasticity within visual cortex. SUMMARY: Collectively, using MRI to investigate the effects on the visual pathway following disease and dysfunction has revealed a rich pattern of results allowing for better characterisation of disease. In the future MRI will likely play an important role in assessing the impact of eye disease on the visual pathway and how it progresses over time

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Understanding Chemistry Of Liquid Fuels Production From Waste Polymer Materials

Liquid fuel production from low density polyethylene thermal decomposition using a Pyroprobe/GC/MS system is reported with a wide range of hydrocarbons comprising major components of gasoline (29.56%), heavy oil (36.03%), jet fuel (17.16%) and diesel (17.26%). The mechanisms of the thermal cracking of LDPE consist of three possible processes: C-C bond breaking, C-H bond breaking and hydrogenation. Due to C-H bond\u27s high bonding energy, the possibility of breaking this bond is less than that of breaking C-C bond. This research focuses on catalyst screening and developing to: (I) reduce the production of heavy oil components; (II) reduce the formation of unsaturated hydrocarbons via hydrogenation; (III) increase the formation of aromatic components to increase the octane number of gasoline. The results indicate that the combination of MgH2 with supported metal catalysts is a promising a catalyst combination for the production of high quality liquid fuels from plastics waste materials

Production Of Fischer-Tropsch Hydrocarbons Via Oxygen-Blown Gasification Of Charred Pinewood Pellets

Thermochemical conversion of biomass to petroleum-equivalent liquid fuels is of particular practical interest since this approach would require practically no changes in existing engine technology and transportation infrastructure. This paper presents results of experimental studies aimed at the producing liquid hydrocarbons (C7 +) via a two-step process: gasification of charred pinewood pellets (CPP) followed by Fischer-Tropsch (FT) synthesis. The gasifier was operated in a semi-continuous updraft mode using a steam-oxygen mixture (in the range of [H2O]/[O2] = 2.2-4.4 mol/mol) as an input oxidizing gas. The effect of gasification parameters, including the rate of oxygen flow and steam/oxygen molar ratio on the syngas yield and composition was determined. It was found that increasing oxygen flow rate into the gasifier (by a factor of 2.3) resulted in higher (by 32%) H2/CO ratio while it had a minor effect on the CO/CO2 ratio in the syngas. Increasing the steam/oxygen ratio led to higher H2/CO ratio in the syngas (up to 2.1 mol/mol) with slight decrease in the gasification rate of CPP. The water consumption rate was significantly reduced at higher steam/oxygen ratios (by almost half at [H2O]/[O2] ratio of 4.4 mol/mol). The syngas from the gasifier was scrubbed of particulate matter and traces of oxygen and dried before it was directed to a FT synthesis reactor. FT synthesis reactor packed with cobalt-based catalyst featuring novel radial-flow design with improved heat-transfer characteristics was employed in this work. The integrated operation of the gasifier and FT reactor yielded mainly C7-C28 straight-chain hydrocarbons. The chain propagation probability (α) of the FT-hydrocarbon products estimated according to Anderson-Schulz-Flory (ASF) distribution model was about 0.8

Production Of Hydrogen And Biofuels Via Thermochemical Processing Of Fast-Growing Aquatic Biomass

The growing demand for clean and sustainable transportation fuels is driving the worldwide R&D efforts aiming at converting biomass to hydrogen and liquid biofuels. Of particular practical interest is the utilization of fast-growing aquatic biomass species that promise much higher products yields per unit of area compared to terrestrial biomass. In this paper, the experimental studies of thermochemical conversion (pyrolysis and gasification) of several aquatic biomass species: microalgae, Lemna minor (duckweed) and azolla, to hydrogen and biofuels are presented. Pyrolysis of the tested samples of aquatic biomass in the range of temperatures 400-700oC yielded pyrolysis gas, biooil and biochar with the distribution of pyrolysis products depending on temperature, residence time and nature of the feedstock. With all the samples, higher process temperature resulted in higher yields of pyrolysis gas and biochar at the expense of biooil. The concentration of hydrogen in duckweed pyrolysis gas increases with temperature and at 700oC it reaches 25 vol.% in raw gas and 42 vol.% after CO2 removal, and it could be further increased to 99 vol.% using off-the-shelf gas separation technology. The analysis of biooil samples indicated that they can be converted to petroleum-equivalent biofuels through existing technological routes such as catalytic hydrodeoxygenation

Pyrolysis Of Fast-Growing Aquatic Biomass - Lemna Minor (Duckweed): Characterization Of Pyrolysis Products

The aim of this work was to conduct the experimental study of pyrolysis of fast-growing aquatic biomass - Lemna minor (commonly known as duckweed) with the emphasis on the characterization of main products of pyrolysis. The yields of pyrolysis gas, pyrolytic oil (bio-oil) and char were determined as a function of pyrolysis temperature and the sweep gas (Ar) flow rate. Thermogravimetric/differential thermogravimetric (TG/DTG) analyses of duckweed samples in inert (helium gas) and oxidative (air) atmosphere revealed differences in the TG/DTG patterns obtained for duckweed and typical plant biomass. The bio-oil samples produced by duckweed pyrolysis at different reaction conditions were analyzed using GC-MS technique. It was found that pyrolysis temperature had minor effect on the bio-oil product slate, but exerted major influence on the relative quantities of the individual pyrolysis products obtained. While, the residence time of the pyrolysis vapors had negligible effect on the yield and composition of the duckweed pyrolysis products. © 2010 Elsevier Ltd

Dual Application Of Duckweed And Azolla Plants For Wastewater Treatment And Renewable Fuels And Petrochemicals Production

Background: Shortages in fresh water supplies today affects more than 1 billion people worldwide. Phytoremediation strategies, based on the abilities of aquatic plants to recycle nutrients offer an attractive solution for the bioremediation of water pollution and represents one of the most globally researched issues. The subsequent application of the biomass from the remediation for the production of fuels and petrochemicals offers an ecologically friendly and cost-effective solution for water pollution problems and production of value-added products. Results: In this paper, the feasibility of the dual application of duckweed and azolla aquatic plants for wastewater treatment and production of renewable fuels and petrochemicals is explored. The differences in absorption rates of the key wastewater nutrients, ammonium and phosphorus by these aquatic macrophytes were used as the basis for optimization of the composition of wastewater effluents. Analysis of pyrolysis products showed that azolla and algae produce a similar range of bio-oils that contain a large spectrum of petrochemicals including straight-chain C10-C21 alkanes, which can be directly used as diesel fuel supplement, or a glycerin-free component of biodiesel. Pyrolysis of duckweed produces a different range of bio-oil components that can potentially be used for the production of green gasoline and diesel fuel using existing techniques, such as catalytic hydrodeoxygenation. Conclusions: Differences in absorption rates of the key wastewater nutrients, ammonium and phosphorus by different aquatic macrophytes can be used for optimization of composition of wastewater effluents. The generated data suggest that the composition of the petrochemicals can be modified in a targeted fashion, not only by using different species, but also by changing the source plants\u27 metabolic profile, by exposing them to different abiotic or biotic stresses. This study presents an attractive, ecologically friendly and cost-effective solution for efficient bio-filtration of swine wastewater and petrochemicals production from generated biomass. © 2014Muradov et al.; licensee BioMed Central Ltd. ©2014 Muradov et al.; licensee BioMed Central Ltd