HIPK2 deficiency causes chromosomal instability by cytokinesis failure and increases tumorigenicity

HIPK2, a cell fate decision kinase inactivated in several human cancers, is thought to exert its oncosuppressing activity through its p53-dependent and -independent apoptotic function. However, a HIPK2 role in cell proliferation has also been described. In particular, HIPK2 is required to complete cytokinesis and impaired HIPK2 expression results in cytokinesis failure and tetraploidization. Since tetraploidy may yield to aneuploidy and chromosomal instability (CIN), we asked whether unscheduled tetraploidy caused by loss of HIPK2 might contribute to tumorigenicity. Here, we show that, compared to Hipk2+/+ mouse embryo fibroblasts (MEFs), hipk2-null MEFs accumulate subtetraploid karyotypes and develop CIN. Accumulation of these defects inhibits proliferation and spontaneous immortalization of primary MEFs whereas increases tumorigenicity when MEFs are transformed by E1A and Harvey-Ras oncogenes. Upon mouse injection, E1A/Ras-transformed hipk2-null MEFs generate tumors with genetic alterations resembling those of human cancers derived by initial tetraploidization events, such as pancreatic adenocarcinoma. Thus, we evaluated HIPK2 expression in different stages of pancreatic transformation. Importantly, we found a significant correlation among reduced HIPK2 expression, high grade of malignancy, and high nuclear size, a marker of increased ploidy. Overall, these results indicate that HIPK2 acts as a caretaker gene, whose inactivation increases tumorigenicity and causes CIN by cytokinesis failure

A fatal case of a paint thinner ingestion: Comparison between toxicological and histological findings

Toluene and xylene are aromatic hydrocarbons commonly used as an industrial solvent for the manufacturing of pharmaceuticals, paints, and chemicals. The Occupational Safety and Health Administration has determined that toluene levels of 2000 parts per million (ppm) are considered dangerous to life and health. Several studies have examined the absorption of toluene and xylene following inhalation and oral ingestion in humans. Volatile organic compounds that are absorbed into the blood are distributed throughout the body; in particular, distribution of absorbed toluene and xylene in humans and rodents is characterized by preferential uptake in well-perfused and lipophil tissues such as the brain, liver, lungs, and body fat and also in central nervous system. The available studies indicate that xylenes are rapidly absorbed independently from the kind of exposition. We illustrate a fatal case of self-poisoning by ingestion of varnishes diluting solvents, reporting the identification and quantification of volatile organic compounds (toluene, o-m-p xylene) from human biologic liquids and viscera samples using the Solid-Phase Microextraction- Headspace-Gas Chromatography/Mass Spectrometry to toxicological analysis, and the histopathological findings evaluated in liver, kidney, and lungs. Copyright © 2010 by Lippincott Williams & Wilkins

Polystyrene Nanoplastics in Aquatic Microenvironments Affect Sperm Metabolism and Fertilization of <i>Mytilus galloprovincialis</i> (Lamark, 1819)

The continuous and unregulated discharge of wastes and pollutants into the aquatic environment has required constant monitoring of the risks incurred by aquatic ecosystems. Alarmism arises from plastic pollution as larger artifacts release nanoscale fragments that can contact free-living stages such as gametes, embryos, and larvae. Specifically, the interaction between spermatozoa, released in water in externally fertilizing species, and the surrounding microenvironment is essential for successful fertilization. Activation and kinematics of movement, proper maintenance of ionic balance, and chemotactism are processes highly sensitive to even minimal perturbations caused by pollutants such as polystyrene nanoplastics. Spermatozoa of Mytilus galloprovincialis (M. galloprovincialis), an excellent ecotoxicological model, undergo structural (plasma membrane ruptures, DNA damage) and metabolic (reduced motility, fertilizing capacity) damage upon exposure to 50 nm amino-modified polystyrene nanoplastics (nPS-NH2). Nanoplastics of larger diameter (100 nm) did not affect sperm parameters. The findings highlighted the negative impact that plastic pollution, related to nanoparticle diameter and concentration, could have on sperm quality and reproductive potential of organisms, altering the equilibrium of aquatic ecosystems

In Vitro Nano-Polystyrene Toxicity: Metabolic Dysfunctions and Cytoprotective Responses of Human Spermatozoa

The ubiquitous spread of Polystyrene nanoplastics (PS-NPs) has rendered chronic human exposure an unavoidable phenomenon. The biodistribution of such particles leads to bioaccumulation in target organs including the testis, the site of sperm maturation. The purpose of this research has been to estimate the impact of PS-NPs (50 and 100 nm) on the metabolism of mature spermatozoa. The analysis of the semen parameters has revealed a higher toxicity of the smaller sized PS-NPs, which have negatively affected major organelles, leading to increased acrosomal damage, oxidative stress with the production of ROS, DNA fragmentation, and decreased mitochondrial activity. PS-NPs of 100 nm, on the other hand, have mainly affected the acrosome and induced a general state of stress. An attempt has also been made to highlight possible protective mechanisms such as the expression of HSP70s and their correlation among various parameters. The results have evinced a marked production of HSP70s in the samples exposed to the smaller PS-NPs, negatively correlated with the worsening in oxidative stress, DNA fragmentation, and mitochondrial anomalies. In conclusion, our results have confirmed the toxicity of PS-NPs on human spermatozoa but have also demonstrated the presence of mechanisms capable of counteracting at least in part these injuries

Plastic additives in commercial fish of Aegean and Ionian Seas and potential hazard to human health

Plastic additives include a wide range of pollutants, added throughout the production process of plastics aiming to improve their properties. Given that they are not chemically bound to the plastic items, they can easily migrate in the marine environment allowing their uptake by marine organisms and accumulation in their tissues. Representatives of Phthalic acid esters (PAEs) and bisphenols have been characterized for their ability to impact not only marine organisms but also humans via fish and seafood consumption. In this study, a liquid-liquid method was applied to determine the concentrations of selected PAEs and Bisphenol A (BPA) in the tissues of E.encrasicolus, S.pilchardus, B.boops, and M.barbatus from two important divisions of fisheries (North Aegean and the Western Ionian Seas, thereof NAS and IOS respectively) of the Mediterranean Sea. The level of contamination varied among the different species and geographical locations. DEHP (bis(2-ethylhexyl) phthalate) had the highest mean concentrations of the examined PAEs for all four species examined. Statistically significant differences in DEHP mean concentrations were observed between the tissues of B.boops (collected from NAS) and S.pilchardus (from IOS) (p &lt; 0.05, Wilcoxon rank test). DIDP (di-isodecyl phthalate) was the following most common PAEs, although no statistically significant differences were presented between sites, species, and tissues. DINP (di-isononyl phthalate) was recorded only in the GIT of E.encrasicolus (from NAS), while the rest of the examined PAEs were presented in a smaller subset of the samples. Noticeably, the parent diester DBP and the metabolic monoester MNBP were concurrently detected in a part of the analyzed samples. The level of risk via fish consumption, based on the Estimated Daily Intake and the Target Hazard Quotient (THQ), showed that the PAEs and BPA had a low likelihood of a negative effect occurring for every scenario that was examined, although THQ for BPA indicated there was a higher likelihood than PAEs of an adverse effect to be presented. The results of this study highlighted the need for future efforts focusing on the factors affecting plastic additives occurrences in the marine environment, especially for marine organisms intended for consumption

Spermiotoxicity of Nano-TiO2 Compounds in the Sea Urchin Paracentrotus lividus (Lamarck, 1816): Considerations on Water Remediation

Despite the great utility of nanoparticles (NPs) in water remediation, their effects on marine ecosystems are unknown and unpredictable. The toxicity of the most used nanoparticles, such as ZnO, Ag, and TiO2 on the purple sea urchin, Paracentrotus lividus (Lamarck, 1816), has been demonstrated by several authors. The aim of this study was to evaluate the effects of TiO2 sol-gel and TiO2-rGO nanocompounds on both vitality and motility of spermatozoa of P. lividus. The spermatozoa were exposed at different times (30 and 60 min) and concentrations (10, 20, 40 &micro;g/mL) of both nano-TiO2 compounds. The results clearly showed a decrease in both vitality and motility of P. lividus spermatozoa exposed. In particular, vitality and motility were inversely related to both exposure time and concentration of TiO2 sol-gel and TiO2-rGO nanocompounds

Attività di ricerca scientifica e Tecnica finalizzate allo Studio di fattibilità per la riapertura dei Navigli Milanesi nell'ambito della riattivazione del sistema complessivo dei Navigli e della sua navigabilità. Coordinatore Antonello Boatti

Il piano di fattibilità per la riapertura dei navigli milanesi Gruppo di ricerca del Politecnico di Milano DAstU (Dipartimento di Architettura e Studi Urbani) Coordinatore Prof. Arch. Antonello Boatti Il piano di fattibilità per la riapertura dei navigli di Milano è una sfida ambiziosa per una città che vuole cambiare nel segno della vivibilità e della sostenibilità, e in particolare per il Milano, che ha basato la sua storia e il suo sviluppo nel corso dei secoli come città d'acqua . I navigli di Milano nel 1619 Lo sfruttamento turistico inerente alla creazione di un sistema continuo di canali e piste ciclabili tra Adda e il Ticino e la reale possibilità di essere in grado di navigare dal Lago Maggiore verso l'Adriatico, ben simboleggia il senso profondo del progetto. La ricerca esplora tutto ciò che può essere coinvolto dalla riapertura del sistema dei navigli a Milano, dal nord -est della città dove il Martesana è ancora aperto, verso il centro della città, dove il canale ritrova il percorso circolare storico (la Cerchia dei Navigli) sul suo lato orientale, fino a raggiungere la Darsena recentemente riattivata per ricongiungersi alla fine con i navigli Pavese e Grande. Il progetto risolve con successo il problema della fornitura di acqua necessaria per garantire la navigabilità per piccole imbarcazioni, anche nel centro di Milano e la riapertura della Cerchia dei Navigli spinge a rinnovare il modello di traffico a Milano con la promozione del trasporto pubblico e della mobilità dolce. E’ stato valutato l'impatto economico del progetto attraverso un’analisi costi-benefici che alla fine ha visto prevalere questi ultimi rispetto ai primi. Infatti si possono sviluppare sinergie positive per la città, dalla produzione di energia con micro turbine, all'utilizzo dell’acqua per le pompe di calore, all'uso degli scavi (che non hanno un impatto negativo dal punto di vista idrogeologico) per migliorare le reti tecnologiche e sviluppare il teleriscaldamento. Inoltre la riapertura dei navigli giocherà un ruolo positivo per il rilancio turistico e commerciale della città. La realizzazione di un’opera di questo tipo deve essere basata su un accurato processo di partecipazione anche eseguendo simulazioni in loco per spiegare gli effetti reali del progetto sulla città. Sono stati effettuati diversi approfondimenti, per esempio presso la Conca dell'Incoronata, alla Conca di Viarenna, nella parte superiore nord di via Melchiorre Gioia, in via San Marco, in Piazza Cavour e in via Molino delle Armi. Questi esempi costituiscono "prototipi" iniziali utili per avviare la realizzazione concreta del progetto di per fasi di attuazione. Fasi di attuazione del progetto Via Melchiorre Gioia Conca dell’incoronata Via San Marco Piazza Cavour Conca di Viarenna Via Molino delle Arm