Investigating Glioblastoma Multiforme Sub-Proteomes: A Computational Study of CUSA Fluid Proteomic Data

Based on our previous proteomic study on Cavitating Ultrasound Aspirator (CUSA) fluid pools of Newly Diagnosed (ND) and Recurrent (R) glioblastomas (GBMs) of tumor core and periphery, as defined by 5-aminolevulinc acid (5-ALA) metabolite fluorescence, this work aims to apply a bioinformatic approach to investigate specifically into three sub-proteomes, i.e., Not Detected in Brain (NB), Cancer Related (CR) and Extracellular Vesicles (EVs) proteins following selected database classification. The study of these yet unexplored specific datasets aims to understand the high infiltration capability and relapse rate that characterizes this aggressive brain cancer. Out of the 587 proteins highly confidently identified in GBM CUSA pools, 53 proteins were classified as NB. Their gene ontology (GO) analysis showed the over-representation of blood coagulation and plasminogen activating cascade pathways, possibly compatible with Blood Brain Barrier damage in tumor disease and surgery bleeding. However, the NB group also included non-blood proteins and, specifically, histones correlated with oncogenesis. Concerning CR proteins, 159 proteins were found in the characterized GBM proteome. Their GO analysis highlighted the over-representation of many pathways, primarily glycolysis. Interestingly, while CR proteins were identified in ND-GBM exclusively in the tumor zones (fluorescence positive core and periphery zones) as predictable, conversely, in R-GBM they were unexpectedly characterized prevalently in the healthy zone (fluorescence negative tumor periphery). Relative to EVs protein classification, 60 proteins were found. EVs are over-released in tumor disease and are important in the transport of biological macromolecules. Furthermore, the presence of EVs in numerous body fluids makes them a possible low-invasive source of brain tumor biomarkers to be investigated. These results give new hints on the molecular features of GBM in trying to understand its aggressive behavior and open to more in-depth investigations to disclose potential disease biomarkers.     

Comprehensive Review Regarding Mercury Poisoning and Its Complex Involvement in Alzheimer’s Disease

Mercury (Hg) is considered one of the most widespread toxic environmental pollutants, which seems to have multiple effects on organisms even at low concentrations. It has a critical role in many health problems with harmful consequences, with Hg primarily targeting the brain and its components, such as the central nervous system (CNS). Hg exposure was associated with numerous CNS disorders that frequently trigger Alzheimer’s disease (AD). Patients with AD have higher concentrations of Hg in blood and brain tissue. This paper aims to emphasize a correlation between Hg and AD based on the known literature in the occupational field. The outcome shows that all these concerning elements could get attributed to Hg. However, recent studies did not investigate the molecular level of Hg exposure in AD. The present review highlights the interactions between Hg and AD in neuronal degenerations, apoptosis, autophagy, oxidative stress (OS), mitochondrial malfunctions, gastrointestinal (GI) microflora, infertility and altering gene expression.     

A Histone Deacetylase (HDAC) Inhibitor with Pleiotropic In Vitro Anti-Toxoplasma and Anti-Plasmodium Activities Controls Acute and Chronic Toxoplasma Infection in Mice

Toxoplasmosis is a highly prevalent human disease, and virulent strains of this parasite emerge from wild biotopes. Here, we report on the potential of a histone deacetylase (HDAC) inhibitor we previously synthesized, named JF363, to act in vitro against a large panel of Toxoplasma strains, as well as against the liver and blood stages of Plasmodium parasites, the causative agents of malaria. In vivo administration of the drug significantly increases the survival of mice during the acute phase of infection by T. gondii, thus delaying its spreading. We further provide evidence of the compound’s efficiency in controlling the formation of cysts in the brain of T. gondii-infected mice. A convincing docking of the JF363 compound in the active site of the five annotated ME49 T. gondii HDACs was performed by extensive sequence–structure comparison modeling. The resulting complexes show a similar mode of binding in the five paralogous structures and a quite similar prediction of affinities in the micromolar range. Altogether, these results pave the way for further development of this compound to treat acute and chronic toxoplasmosis. It also shows promise for the future development of anti-Plasmodium therapeutic interventions.     

Sustainability assessment of energy technologies via social indicators: Results of a survey among European energy experts

Sustainability assessment of energy technologies oftentimes fails to account for social repercussions and long-term negative effects and benefits of energy systems. As part of the NEEDS¹ project, an expert-based set of social indicators was developed and verified by the European stakeholders with the objective of contributing in the development of social indicators for the assessment of societal effects of energy systems. For this purpose, scientific experts from four sample countries France, Germany, Italy and Switzerland were interviewed to assess 16 different energy systems on a specific stakeholder reviewed indicator set. The indicator set covers the four main criteria: “security and reliability of energy provision; “political stability and legitimacy”; “social and individual risks” and “quality of life”. This article will review the process of indicator development and assessment and highlight results for today's most prominent and future energy technologies and some likely to make an impact in the future. Expert judgments varied considerably between countries and energy systems, with the exception of renewable technologies, which were overall positively assessed on almost all evaluation criteria.     

Stereochemistry-dependent inhibition of RAS farnesylation by farnesyl phosphonic acids

This investigation compares the effects of three farnesyl pyrophosphate analogs on selected aspects of isoprenoid metabolism. E,E-α-Hydroxyfarnesylphosphonate was prepared by an improved variation on a literature synthesis, which also gave access to the new Z,E-α-hydroxyfarnesyl- and α-hydroxygeranylphosphonates. A striking find is that only E,E-α-hydroxyfarnesylphosphonate induces alteration of RAS processing in intact human-derived leukemia cells and inhibits farnesyl protein transferase in enzyme assays, while the Z,E-α-farnesyl- and geranylphosphonates are inactive. The inhibitory activity of E,E-α-hydroxyfarnesylphosphonate is greater in enzyme than intact cell assays. This active compound does not significantly inhibit geranylgeranyl protein transferase I or squalene synthase, nor does it diminish cholesterol synthesis. These results indicate that the length of the terpenoid chain and olefin stereochemistry allow selective inhibition of critical enzymes of terpenoid metabolism. Discrimination was observed between inhibition of farnesyl protein transferase and squalene synthase by E,E-α-hydroxyfarnesylphosphonate, even though both enzymes utilize farnesyl pyrophosphate as their natural substrate.     

Dynamic response of transiently trapped entanglements in polymer networks

The structure and viscoelastic response of polymer networks are highly sensitive to the presence of pendant chains. These imperfections, that are unavoidable produced during a cross-linking reaction, reduce the cross-linking density and affect the damping response of elastomers. In this work the dynamics of pendant chains present in a cross-linked network is investigated using end-linked poly(dimethyl-siloxane) networks with well defined structure. For this purpose, model networks containing 10 and 20 wt% of two different monodisperse pendant chains with molecular weights well above the critical entanglement molecular weight and some of their blends were prepared. It was found that, within this range of concentration of pendant chains, the long-time dynamic response of the networks was nearly insensitive to the content of pendant material but deeply influenced by the average molar mass of these defects. While the equilibrium behavior of the networks can be well described by a mean field theory for rubber elasticity, the long time relaxational dynamics can be rationalized in terms of the Pearson-Helfand picture for the arm retraction process. Within this theoretical picture, the dynamics can be explained in terms of the molecular architecture of the network, the Rouse time and the weight average molar mass of the pendant material.     

Catalytic Wet Air Oxidation of Aqueous Solutions of Substituted Phenols

Catalytic wet air oxidation (CWAO) of aqueous solutions of phenol, 2-chlorophenol and 4-nitrophenol were studied using Cu/CeO₂ with 4% of copper as catalytic material. The catalyst was prepared by an impregnation method and characterized by X-ray diffraction (XRD), BET surface area, oxygen storage capacity (OSC), temperature programmed reduction (TPR), electron paramagnetic resonance (EPR) and XPS. The reaction was carried out in a batch reactor at T=160 °C and 1.0 MPa. Cu/CeO₂ catalyst was found effective in CWAO. On the basis of characterization data, it is suggested that the high activity of the copper–ceria catalyst is related to the modification of the structural and redox properties of the cerium oxide on copper addition. The ratio BOD₅/COD was measured to evaluate the biodegradability. Pretreatment by CWAO under operating conditions resulted in effluents whose biodegradation rates were significantly higher than those of the original.     

High modulus polypropylene fibers. II. Influence of fiber preparation upon structure and morphology

The influence of drawing on the limiting draw ratio upon formation of the morphological structure of fibers spun from binary polypropylene (PP) blends was studied. Fibers were spun from a fiber‐grade CR‐polymer and from the blends of a fiber‐grade CR‐polymer with a molding‐grade polymer in the composition range of 10–50 wt % added. As‐spun fibers were immediately moderately and additionally highly drawn at the temperature of 145°C. The structure and morphology of these fibers were investigated by small‐angle X‐ray scattering, wide‐angle X‐ray scattering, differential scanning calorimetry, scanning electron microscopy, density, birefringence, and sound velocity measurements. It was shown that continuously moderately drawn fibers are suitable precursors for the production of high tenacity PP fibers of very high modulus, because of so called oriented “smectic” structure present in these fibers. With drawing at elevated temperature, the initial metastable structure of low crystallinity was disrupted and a c‐axis orientation of monoclinic crystalline modification was developed. Hot drawing increased the size of crystallites and crystallinity degree, the orientation of crystalline domains, and average orientation of the macromolecular chains and resulted in extensive fibrillation and void formation. It was found that the blend composition has some influence on the structure of discontinuously highly drawn fibers. With increasing the content of the molding‐grade polymer in the blend, the size of crystalline and amorphous domains, density and crystallinity, as well as amorphous orientation decreased. Relationship has been established between the mechanical properties, crystallinity, and orientation of PP fibers. It was confirmed that by blending the fiber‐grade CR‐polymer by a small percentage of the molding‐grade polymer, maximization of elastic modulus is achieved, mainly because of higher orientation of amorphous domains. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 1067–1082, 2006     

Effects of coal syngas and H2S on the performance of solid oxide fuel cells: Part 2. Stack tests

The performance of two-cell planar solid oxide fuel cell stacks using coal syngas, with and without hydrogen sulfide (H₂S), was studied. All cells were tested at 850 °C with a constant current load of 15.2 A (current density of 0.22 A cm⁻² per cell) and 30% fuel utilization. The H₂S injection immediately and significantly affected the power degradation of the stack system regardless of the carrier fuel. Results for the test with only H₂ and N₂ in the presence of H₂S (119–120 ppm) indicated that the power decay and area-specific resistance (ASR) degradation values were lower than those for the tests where simulated syngas containing CO and increased water content was used. The results indicate that contact points in the stack contributed to the power degradation of the system. Other factors, including contamination from the upstream fuel gas tubing, may have contributed to the higher degradation under simulated syngas conditions. In general the data confirm previous results for single cell testing, and showed that for this specific short stacks (two-cells) arrangement both a fast and a slow response to H₂S injection that eventually stabilized.     

Biomarker Associations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

The prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH) is heavily influenced by the development of delayed cerebral ischemia (DCI), but the adequate and effective therapy of DCI to this day has not been resolved. Multiplex serum biomarker studies may help to understand the pathophysiological processes underlying DCI. Samples were collected from patients with aSAH at two time points: (1) 24 h (Day 1) and (2) 5–7 days after ictus. Serum concentrations of eotaxin, FGF-2, FLT-3L, CX3CL1, Il-1b, IL-4, IP-10, MCP3, and MIP-1b were determined using a customized MILLIPLEX Human Cytokine/Chemokine/Growth Factor Panel A multiplex assay. The functional outcome was defined by the modified Rankin scale (favorable: 0–2, unfavorable: 3–6) measured on the 30th day after aSAH. One-hundred and twelve patients with aSAH were included in this study. The median level of CX3CL1 and MCP-3 measured on Days 5–7 were significantly higher in patients with DCI compared with those without DCI (CX3CL1: with DCI: 110.5 pg/mL, IQR: 82–201 vs. without DCI: 82.6, 58–119, p = 0.036; and MCP-3: with DCI: 22 pg/mL (0–32) vs. without DCI: 0 (0–11), p < 0.001). IP-10, MCP-3, and MIP-1b also showed significant associations with the functional outcome after aSAH. MCP-3 and CX3CL1 may play a role in the pathophysiology of DCI.