STAT3, a hub protein of cellular signaling pathways, is triggered by β-hexaclorocyclohexane

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 µM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect

QCALT: a tile calorimeter for KLOE-2 upgrade

The upgrade of the DA$\Phi$NE machine layout requires a modification of the size and position of the inner focusing quadrupoles of KLOE-2 thus asking for the realization of two new calorimeters covering the quadrupoles area. To improve the reconstruction of $K_L\to 2\pi^0$ events with photons hitting the quadrupoles a calorimeter with high efficiency to low energy photons (20-300 MeV), time resolution of less than 1 ns and space resolution of few cm, is needed. To match these requirements, we are designing a tile calorimeter, QCALT, where each single tile is readout by mean of SiPM for a total granularity of 2400 channels. We show first tests of the different calorimeter components

Effects of abiotic stressors on lutein production in the green microalga Dunaliella salina.

BackgroundRecent years have witnessed a rising trend in exploring microalgae for valuable carotenoid products as the demand for lutein and many other carotenoids in global markets has increased significantly. In green microalgae lutein is a major carotenoid protecting cellular components from damage incurred by reactive oxygen species under stress conditions. In this study, we investigated the effects of abiotic stressors on lutein accumulation in a strain of the marine microalga D. salina which had been selected for growth under stress conditions of combined blue and red lights by adaptive laboratory evolution.ResultsNitrate concentration, salinity and light quality were selected as three representative influencing factors and their impact on lutein production in batch cultures of D. salina was evaluated using response surface analysis. D. salina was found to be more tolerant to hyper-osmotic stress than to hypo-osmotic stress which caused serious cell damage and death in a high proportion of cells while hyper-osmotic stress increased the average cell size of D. salina only slightly. Two models were developed to explain how lutein productivity depends on the stress factors and for predicting the optimal conditions for lutein productivity. Among the three stress variables for lutein production, stronger interactions were found between nitrate concentration and salinity than between light quality and the other two. The predicted optimal conditions for lutein production were close to the original conditions used for adaptive evolution of D. salina. This suggests that the conditions imposed during adaptive evolution may have selected for the growth optima arrived at.ConclusionsThis study shows that systematic evaluation of the relationship between abiotic environmental stresses and lutein biosynthesis can help to decipher the key parameters in obtaining high levels of lutein productivity in D. salina. This study may benefit future stress-driven adaptive laboratory evolution experiments and a strategy of applying stress in a step-wise manner can be suggested for a rational design of experiments

Improvement of Tuberculosis Laboratory Capacity on Pemba Island, Zanzibar: A Health Cooperation Project.

Low-income countries with high Tuberculosis burden have few reference laboratories able to perform TB culture. In 2006, the Zanzibar National TB Control Programme planned to decentralize TB diagnostics. The Italian Cooperation Agency with the scientific support of the "L. Spallanzani" National Institute for Infectious Diseases sustained the project through the implementation of a TB reference laboratory in a low-income country with a high prevalence of TB. The implementation steps were: 1) TB laboratory design according to the WHO standards; 2) laboratory equipment and reagent supplies for microscopy, cultures, and identification; 3) on-the-job training of the local staff; 4) web- and telemedicine-based supervision. From April 2007 to December 2010, 921 sputum samples were received from 40 peripheral laboratories: 120 TB cases were diagnosed. Of all the smear-positive cases, 74.2% were culture-positive. During the year 2010, the smear positive to culture positive rate increased up to 100%. In March 20, 2010 the Ministry of Health and Social Welfare of Zanzibar officially recognized the Public Health Laboratory- Ivo de Carneri as the National TB Reference Laboratory for the Zanzibar Archipelago. An advanced TB laboratory can represent a low cost solution to strengthen the TB diagnosis, to provide capacity building and mid-term sustainability

The Low Energy Tagger for the KLOE-2 experiment

The KLOE experiment at the upgraded DAFNE e+e- collider in Frascati (KLOE-2) is going to start a new data taking at the beginning of 2010 with its detector upgraded with a tagging system for the identification of gamma-gamma interactions. The tagging stations for low-energy e+e- will consist in two calorimeters The calorimeter used to detect low-energy e+e- will be placed between the beam-pipe outer support structure and the inner wall of the KLOE drift chamber. This calorimeter will be made of LYSO crystals readout by Silicon Photomultipliers, to achieve an energy resolution better than 8% at 200 MeV.Comment: 4 pages, 5 figures, in the proceedings of "Frontier detectors for frontier physics", isola d'Elba, Italy, May 200

A remembrance of things (best) forgotten: The 'allegorical past' and the feminist imagination

This is the author's PDF version of an article published in Feminist theology© 2012. The definitive version is available at http://fth.sagepub.com/This article discusses the US TV series Mad Men, which is set in an advertising agency in 1960s New York, in relation to two key elements which seem significant for a consideration of the current state of feminism in church and academy, both of which centre around what it means to remember or (not) to forget

Measurement and Processing of Road Irregularity for Surface Generation and Tyre Dynamics Simulation in NVH Context

Nowadays, finite element tyre models are often used to perform vehicle NVH (noise, vibration, harshness) simulations. To account for the specific operating conditions, a road surface must be properly included in the model. This paper deals with a methodology to experimentally evaluate and process road irregularity measurements, so as to generate a road surface input. These surfaces are used to simulate the tyre/road interaction at the footprint, which is modelled as a contact surface in finite element tyre models. For this reason, a linear profile of the road surface is not suitable for these simulations and the whole surface must be considered. Starting from the measurements taken through a test equipment specifically designed to carry laser sensors and scan road profiles, the Power Spectral Density (PSD) of a specific track is estimated and then interpolated considering piecewise functions. Finally, a model to generate a road surface starting from the measured PSD is developed, discussed and validated

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent

Defective Erythrocyte Pyruvate Kinase with Impaired Kinetics and Reduced Optimal Activity

A unique mutant form of erythrocyte pyruvate kinase has been found associated with chronic haemolytic anaemia in a child who is apparently doubly heterozygous for the mutant isoenzyme and for pyruvate kinase deficiency of the classical quantitative type. Clinical and laboratory findings conformed closely to those typically observed in homozygous pyruvate kinase deficiency anaemia. Assayed in fresh haemolysates, the isoenzyme exhibited reduced optimal activity ( c 45% of normal) and an increased Michaelis constant for phosphoenolpyruvate (four to five times greater than normal). The kinetic anomaly was only partially corrected by activation with fructose-1,6-disphosphate. Despite some common characteristics, this isoenzyme appears distinct from others reported in the literature and lends support to the polymorphous nature of heritable baemolytic anaemias secondary to defective pyruvate kinase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73844/1/j.1365-2141.1972.tb05713.x.pd

Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway

The angiopoietin-like 4 (ANGPTL4) protein belongs to a superfamily of secreted proteins structurally related to factors modulating angiogenesis known as angiopoietins. At first, ANGPTL4 has been identified as an adipokine exclusively involved in lipid metabolism, because of its prevalent expression in liver and adipose tissue. This protein regulates lipid metabolism by inhibiting lipoprotein lipase (LPL) activity and stimulating lipolysis of white adipose tissue (WAT), resulting in increased levels of plasma triglycerides (TG) and fatty acids. Subsequently, ANGPTL4 has been shown to be involved in several nonmetabolic and metabolic conditions, both physiological and pathological, including angiogenesis and vascular permeability, cell differentiation, tumorigenesis, glucose homoeostasis, lipid metabolism, energy homeostasis, wound healing, inflammation, and redox regulation. The transcriptional regulation of ANGPTL4 can be modulated by several transcription factors, including PPAR\uce\ub1, PPAR\uce\ub2/\uce\ub4, PPAR\uce\ub3, and HIF-1\uce\ub1, and nutritional and hormonal conditions. Several studies showed that high levels of ANGPTL4 are associated with poor prognosis in patients with various solid tumors, suggesting an important role in cancer onset and progression, metastasis, and anoikis resistance. Here, we have discussed the potential role of ANGPTL4 in mediating the cross talk between metabolic syndromes, such as diabetes and obesity, and cancer through regulation of its expression by PPARs