Inhibition of Soluble Epoxide Hydrolase Ameliorates Phenotype and Cognitive Abilities in a Murine Model of Niemann Pick Type C Disease

Niemann–Pick type C (NPC) disease is a rare autosomal recessive inherited childhood neurodegenerative disease characterized by the accumulation of cholesterol and glycosphingolipids, involving the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 12-diols, exerts beneficial effects in modulating inflammation and autophagy, critical features of the NPC disease. This study aims to evaluate the effects of UB-EV-52, an sEH inhibitor (sEHi), in an NPC mouse model (Npc) by administering it for 4 weeks (5 mg/kg/day). Behavioral and cognitive tests (open-field test (OF)), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that the treatment produced an improvement in short- and long-term memory as well as in spatial memory. Furthermore, UB-EV-52 treatment increased body weight and lifespan by 25% and reduced gene expression of the inflammatory markers (i.e., Il-1β and Mcp1) and enhanced oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. As for autophagic markers, surprisingly, we found significantly reduced levels of LC3B-II/LC3B-I ratio and significantly reduced brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in treated Npc mice group compared to untreated ones in hippocampal tissue. Lipid profile analysis showed a significant reduction of lipid storage in the liver and some slight changes in homogenated brain tissue in the treated NPC mice compared to the untreated groups. Therefore, our results suggest that pharmacological inhibition of sEH ameliorates most of the characteristic features of NPC mice, demonstrating that sEH can be considered a potential therapeutic target for this disease.     

Hydrogen storage performance of methyl-substituted mesoporous silica with tailored textural characteristics

Journal of Porous Materials - The present study reports a systematic analysis of morphology and hydrogen sorption capacity of mesoporous organic-inorganic silica prepared by varying the silica...     

“Laboratorio Q”, Seville: creative production of collective spaces before and after austerity

The creative city approach is going through a redefinition after the 2008 global financial crisis. In the specific case of South-European cities, in the context of austerity and cuts in public investment, creativity is becoming a strategy for achieving maximum social benefit and improvement of the built environment with minimum economic expenditure. This paper looks at this redefinition of creativity through the case study of Seville, in southern Spain. Through research methods that include video-recorded testimonies of the actors involved, mapping at the online platform “Laboratorio Q”, and public engagement activities, this paper explores how the civic society, professional, and public authorities have reinvented how to produce collective spaces. The paper concludes that bottom-up creative processes for producing collective spaces have become more visible since the 2008 crisis, when architects, planners, public authorities and policy-makers have been “learning” from them.     

A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic Acid

Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C₃OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.     

Rapid Synthesis and Antiproliferative Properties of Polyazamacrocycle-Based Bi- and Tetra-Gold(I) Phosphine Dithiocarbamate Complexes

A family of bi- and tetrametallic gold(I) phosphine dithiocarbamate complexes were synthesized, starting from cyclam and dimethylcyclam polyazamacrocycles, respectively, along with their monometallic gold(I) chloridophosphine precursors. Their antiproliferative properties were evaluated on two cancer cell lines (A549 and NSCLC-N6-L16). Most of the mono- and bimetallic complexes displayed strong activities and, in particular, one bimetallic derivative showed antiproliferative properties in the low micromolar range. Insights into the structure–activity relationships are given, along with determination of the thioredoxin reductase inhibition potential, two-photon imaging of the fluorescent derivatives, and evaluation of gold uptake.     

The Photomontage Activity of Postmodernism

For decades now, Douglas Crimp’s landmark 1980 essay ‘The Photographic Activity of Postmodernism’ has shaped our understanding of modernism’s aftermath, at least as it unfolded in North America and Western Europe. Less remembered, however, is the degree to which the procedures of disjunction, copying, appropriation, and outright theft that he highlighted were epitomised not just by contemporary photography, but by photomontage in particular. This article recovers the debates that led critics such as Crimp, Abigail Solomon-Godeau, Christopher Phillips, Benjamin Buchloh and others to turn to photomontage as one of their principal objects of concern in what became known as the postmodern critique of photography. Why was montage tasked to perform this critical function, particularly by people around the journal October who had not otherwise devoted the balance of their writing to photography’s history? The article suggests that these men and women, along with the contemporary artists they foregrounded, manifested what Mary Anne Doane has called a ‘desire for signification’, a reaction in the late 1970s against the mute theatricality of minimalist and conceptual art. Photomontage reintroduced representation to contemporary art and to the canon of art history. But unlike the reemerging illusionism in painting that also manifested this desire, montage guarded against an uncomplicated realism by highlighting and critiquing operations of representation in a manner that painting no longer could.     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

Risk factors in software development projects: a systematic literature review

Software Quality Journal - Risks are an inherent part of any software project. The presence of risks in environments of software development projects requires the perception so that the associated...     

Influence of temperature cycling and pore fluid on tensile strength of chalk

Calcite has a highly anisotropic thermal expansion coefficient, and repeated heating and cooling cycles can potentially destabilize chalks by breaking cement bonds between neighboring particles. Based on tensile strength measurements, we investigated how temperature cycles induce weakening of chalk. Tensile strength tests were performed on chalk specimens sampled from Kansas (USA) and Mons (Belgium), each with differing amounts of contact cement. Samples of the two chalk types were tested in dry and water-saturated states, and then exposed to 0, 15, and 30 temperature cycles in order to find out under what circumstances thermally induced tensile strength reduction occurs. The testing results show that the dry samples were not influenced by temperature cycling in either of the chalk types. However, in the water-saturated state, tensile strength is increasingly reduced with progressive numbers of temperature cycles for both chalk samples, especially for the more cemented Kansas chalk. The Kansas chalk demonstrated higher initial tensile strength compared to the less cemented Mons chalk, but the strength of both chalks was reduced by the same relative proportion when undergoing thermal cycles in the water-saturated state.