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This study presents a modelling system to evaluate the impact of weight reduction in light commercial vehicles with diesel engines on air quality and greenhouse gas emissions. The PROPS model assesses the emissions of one vehicle in the aforementioned category and its corresponding reduced-weight version. The results serve as an input to the RIAT+ tool, an air quality integrated assessment modelling system. This paper applies the tools in a case study in the Lombardy region (Italy) and discusses the input data pre-processing, the PROPS-RIAT+ modelling system runs, and the results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Inorganic arsenic (iAs) is a human carcinogen, well known as a clastogenic compound. To evaluate the molecular mechanism of arsenite (iAs(III)) toxicity, we investigated the effects on cell growth and apoptosis, telomere length, telomerase expression, as well as the formation of reactive oxygen species (ROS) in male and female human cord blood cells in vitro. Incubation with iAs(III) at the concentration of 0.0001 microM increased telomerase mRNA and protein expression maintained both telomere length and cellular growth, and induced mRNA over-expression of the two oncogenes ras and myc. Our results suggest that female cord blood cells are more sensitive than male ones to iAs(III) induced telomerase stimulation at low concentrations, possibly related to the increased expression of ras and myc oncogenes. On the contrary, at the concentration of 1 microM, iAs(III) decreased telomerase expression and telomere length, and induced apoptosis, necrosis and production of reactive oxygen species. Buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, markedly increased the percentage of apoptotic cells, suggesting that GSH is fundamental for detoxification of iAs(III) in cord blood cells. The reactive oxygen species (ROS) scavenger, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), protected cord blood cells from iAs(III) toxicity, and prevented telomere shortening and telomerase down-modulation. It can be concluded that telomerase expression and telomere length are associated with iAs(III) induced cell death, via production of reactive oxygen species, as well as with iAs(III) induced effects on cell differentiation processes and rate of cell growth.

The effects of arsenate (As) and atrazine (Atr) on myeloid progenitors (colony-forming unit-granulocyte/macrophage, CFU-GM) cells derived from bone marrow were studied in male and female mice after combined in utero and juvenile exposure. Female adult mice were treated with arsenate in drinking water during gestation. Then, separate groups of males and females' offspring were exposed for 4 months to atrazine, to additional arsenate or to co-exposure of atrazine and arsenate together in drinking water. In male mice, arsenate and the combined exposure did not modulate the percentage of CFU-GM progenitors, whereas atrazine significantly decreases the clonogenicity of myeloid cells. In females, the percentage of CFU-GM significantly decreased after atrazine exposure did not change with arsenate treatment, but dramatically increased after the combined exposure. The expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in bone marrow cells was investigated, and an up-regulation of receptor beta was observed in both genders. A gene expression profile was generated using nylon membranes spotted with 1185 cancer-related genes. Results from microarrays indicate that atrazine alone did not stimulate the expression of any of the genes analysed in both male and female. Arsenic induced gene expression modulation only in female. Major significant changes on the gene expression resulted following the co-exposure to arsenic and atrazine in both male and female.

Inorganic arsenic (iAs) and its metabolites are transferred to the foetus through the placental barrier and this exposure can compromise the normal development of the unborn. For this reason, we assessed the toxicity of sodium arsenite (iAs(III)) and its metabolites dimethylarsinic acid (DMA(V)), monomethylarsonic acid (MMA(V)) and monomethylarsonous acid (MMA(III)) on human haematopoietic cord blood cells and murine bone marrow progenitors in vitro, looking at the effects induced at different concentrations in the two genders. The expression of two enzymes responsible for arsenic biotransformation arsenic methyltranferase (AS3MT) and glutathione S-transferase omega 1 (GSTO1) was evaluated in human cord blood cells. Cord blood and bone marrow cells were exposed in vitro to iAs(III) at a wide range of concentrations: from 0.0001 microM to 10 microM. The methylated arsenic metabolites were tested only on human cord blood cells at concentrations ranging from 0.00064 microM to 50 microM. The results showed that iAs(III) was toxic on male and female colony forming units to about the same extent both in human and in mouse. Surprisingly, very low concentrations of iAs(III) increased the proliferation rate of both human and murine female cells, while male cells showed no significant modulation. MMA(V) and DMA(V) did not exert detectable toxicity on the cord blood cells, while MMA(III) had a marked toxic effect both in male and female human progenitors. AS3MT mRNA expression was not induced in human cord blood cells after iAs(III) exposure. GSTO1 expression decreased after MMA(III) treatment. This study provides evidence that exposure to iAs(III) and MMA(III) at muM concentrations is associated with immunosuppression in vitro.

Organotins are widely used in agriculture and the chemical industry, causing persistent and widespread pollution. Organotins may affect the brain, liver and immune system and eventually human health. Recently, it has been shown that tri-butyltin (TBT) interacts with nuclear receptors PPAR gamma (peroxisome proliferator-activated receptor gamma) and RXR (retinoid x receptor) leading to adipocyte differentiation in the 3T3 cell line. Since adipocytes are known to influence haematopoiesis, for instance through the expression of cytokines and adhesion molecules, it was considered of interest to further study the adipocyte-stimulating effect of TBTC in human bone marrow cultures. Nile Red spectrofluorimetric analysis showed a significant increase of adipocytes in TBTC-treated cultures after 14 days of long term culture. Real-time PCR and Western blot analysis confirmed the high expression of the specific adipocyte differentiation marker aP2 (adipocyte-specific fatty acid binding protein). PPAR gamma, but not RXR, mRNA was increased after 24 h and 48 h exposure. TBTC also induced a decrease in a number of chemokines, interleukins, and growth factors. Also the expression of leptin, a hormone involved in haematopoiesis, was down regulated by TBTC treatment. It therefore appears that TBTC induced adipocyte differentiation, whilst reducing a number of haematopoietic factors. This study indicates that TBTC may interfere in the haematopoietic process through an alteration of the stromal layer and cytokine homeostasis.

Alpha-glycosyl ureas can be synthesised directly from tetra-O-benzyl glycosyl azides and isocyanates, using a one-pot procedure that is simple and general in scope. The benzyl protecting groups are easily removed from the urea products by catalytic hydrogenation. The synthesised alpha-glycosyl ureas represent a new class of neo-glycoconjugates with the potential of being resistant towards carbohydrate processing enzymes.