Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

Challenges in the Application of Stochastic Modal Identification Methods to a Cable-Stayed Bridge

This paper presents an analysis of the data collected in the ambient vibration test of the International Guadiana cable-stayed Bridge, which links Portugal and Spain, based on different output-only identification techniques: peak-picking, frequency domain decomposition, covariance-driven stochastic subspace identification, and data-driven stochastic subspace identification. The purpose of the analysis is to compare the performance of the four techniques and evaluate their efficiency in dealing with specific challenges involved in the modal identification of the tested cable-stayed bridge, namely the existence of closely spaced modes, the perturbation produced by the local vibration of stay-cables, and the variation of modal damping coefficients with wind velocity. The identified natural frequencies and mode shapes are compared with the corresponding modal parameters provided by a previously developed numerical model. Additionally, the variability of some modal damping coefficients is related with the variation of the wind characteristics and associated with a component of aerodynamic damping.     

Syllables as processing units in handwriting production.

This research focused on the syllable as a processing unit in handwriting. Participants wrote, in uppercase letters, words that had been visually presented. The interletter intervals provide information on the timing of motor production. In Experiment 1, French participants wrote words that shared the initial letters but had different syllable boundaries. In Experiment 2, French- and Spanish-speaking participants wrote cognates and pseudowords with a letter sequence that was always intrasyllabic in French and intersyllabic in Spanish. In Experiment 3, French-Spanish bilinguals wrote the cognates and pseudowords with the same type of sequences. In the 3 experiments, the critical interletter intervals were longer between syllables than within syllables, indicating that word syllable structure constrains motor production both in French and Spanish. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Polymerization strategies to overcome limiting monomer conversion in silicone-acrylic miniemulsion polymerization

The limiting conversion phenomenon observed in high solid content silicone-modified acrylic miniemulsion polymerizations was investigated. It was found that the limiting conversion was mainly due to the formation of inactive radicals upon propagation of butyl acrylate radicals with the vinyl end groups of the polydimethylsiloxane. Polymerization strategies that allowed overcoming this problem and achieving high monomer conversion were implemented.     

Dogs (Canis familiaris) learn their owners via observation in a manipulation task.

Eighty-seven pet dogs (Canis familiaris) were involved in an experiment in which they had to solve a task to obtain a ball. After witnessing a full demonstration by their owner (10 times pushing the handle of the box, which released a ball), most dogs preferred to touch the handle sooner and more frequently in comparison with other parts of the box, and they used the handle to get the ball. In contrast dogs in 3 control groups developed their own respective methods. The lack of emergence of the ball and playing after the demonstration did not affect the learning performance strongly. This suggests that in dogs the outcome of a demonstration plays only a restricted role in the manifestation of social learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.     

Integrating supercomputing clusters into education: a case study in biotechnology

The Journal of Supercomputing - The integration of a Supercomputer in the educational process improves student’s technological skills. The aim of the paper is to study the interaction between...