Mycotoxins nivalenol and deoxynivalenol differently modulate cytokine mRNA expression in Jurkat T cells.

Deoxynivalenol (DON) and its hydroxylated form nivalenol (NIV) are Fusarium mycotoxins that occur in cereal grains alone or in combination. Several studies have shown that these metabolites affect lymphocyte functions. However, the molecular mechanisms underlying their activities are still partially known. To address this issue, we examined the influence of NIV and DON in modulating IFNc, IL-2 and IL-8 mRNA levels in Jurkat T cells. In PMA/ionomycin stimulated cells, pre-incubated with increasing concentrations of NIV, transcription was induced in the range 0.06–2 lM; higher concentrations of NIV were found non-stimulating (4 lM) or inhibitory (8 lM) for IFNc and IL-2 whereas IL-8 was still induced. DON administration elicited a similar profile for IL-8 and IFNc, whilst IL-2 mRNA was induced in a broader range of concentrations. Combination of NIV and DON at 1:1 and 1:10 ratios essentially restored the cytokine transcriptional pattern observed with NIV alone but the level of transcripts, with the exception of IL-8, peaked at lower concentrations suggesting interactive effects. Moreover both mycotoxins caused inhibition of cell proliferation, mediated by induction of apoptosis, confirming previous results and highlighting the usefulness of Jurkat as a T-cell model to study the effects of mycotoxins on the immune functions in humans

CT-based tumour response criteria compared after combined treatment for liver metastases of colorectal cancer

open6noPurpose: The aim of this analysis is to compare different tumour response criteria (TRC) after chemotherapy combined with bevacizumab in liver metastases from colorectal cancer (mCRC) to ascertain the best early prognostic indicator of response. Methods and Materials: 103 target liver metastases from 65 mCRC patients treated with chemoterapy plus bevacizumab were examined at the Istituto Oncologico Veneto IOV-IRCSS (March 2008-January 2013). All patients had baseline CT and at least one follow-up scan. Tumour response was retrospectively analyzed by two radiologists using RECIST1.1, modified Choi, and Chun morphologic criteria. Tumour response, classified as good (complete or partial response) or poor (stable or progressive disease), was compared with progression-free survival (PFS) at first follow-up (t1) and time of best response. Interobserver agreement and concordance between TRC were measured. Results: At t1, 32.31% showed a good response according to RECIST1.1 (median PFS 11.1), 84.62% according to Choi (median PFS 10.8). These percentages rose to 49.23% (median PFS 12.1) and 87.69% (median PFS 10.8), respectively, at the time of best response. According to Chun, 67.69% showed a good response at the time of best response (median PFS 10.8). The Choi criteria detected a higher proportion of good responders at t1, showing a better correlation with PFS; all methods correlated with PFS at the time of best response. Conclusion: The Choi criteria proved more consistent in the early detection of response in mCRC treated with chemotherapy plus bevacizumab, underscoring the importance of using these criteria in the early assessment of response to combined treatment.openopenVarotto, A.; Di Grazia, L.; Aliberti, C.; Bergamo, F.; Nardin, M.; Pomerri, F.Varotto, A.; Di Grazia, L.; Aliberti, C.; Bergamo, F.; Nardin, M.; Pomerri, Fabi

Influence of components of tumour microenvironment on the response of HCT-116 colorectal cancer to the ruthenium-based drug NAMI-A

Solid tumours are constituted of tumour cells, healthy cells recruited from the host tissues and soluble factors released by both these cell types. The present investigation examines the capacity of co-cultures between the HCEC colon epithelial cells and the HCT-116 colorectal cancer cells (mimicking the primary site of tumour growth) and between IHH hepatocytes and the HCT-116 colorectal cancer cells (metastatic site) to influence the effects of NAMI-A (imidazolium trans-imidazoledimethylsulphoxidetetrachloro ruthenate) on the tumour cells themselves. The growth of HCT-116 cells is significantly influenced when the cancer cells are sown on a monolayer of HCEC. The release of soluble factors by the healthy cells promotes, in HCT-116 colorectal cancer cells, the transcription of genes involved in growth, invasion and migration. NAMI-A is not cytotoxic to HCT-116 cells grown on plastics or co-cultured with HCEC or IHH cells, and maintains its ability to control the cell pseudo-metastatic ability, mimicked by the migration in the scratch test. The effects of NAMI-A on HCT-116 migration are supported by its inhibition of the transcription of the ABL-2, ATF-3 and RND-1 genes. In conclusion the study highlights the need of test systems more complex than a single cancer cell culture to study an anticancer drug in vitro and reinforces the hypothesis that NAMI-A targets the ability of the cancer cell to interact with the tumour microenvironment and with the signals that support its metastatic ability

Direct radiative effects by anthropogenic particles at a polluted site: Rome (Italy)

The direct radiative effect (DRE) by all (anthropogenic plus natural) and anthropogenic aerosols is calculated at the solar (0.3–4 μm) and infrared (4–200 μm) spectral range to better address the annual cycle of the anthropogenic aerosol impact at a site (Rome, Italy) significantly affected by pollution. Aerosol optical and microphysical properties from 2003 AERONET Sun/sky-photometer measurements and solar surface albedos based on MODIS satellite sensor data constitute the necessary input to radiative transfer simulations. Clear- and all-sky conditions are investigated by adopting ISCCP monthly products for high-, mid-, and low-cloud cover. It is shown that monthly mean values of aerosol optical depths by anthropogenic particles (AODa) are on average more than 50% of the corresponding all-aerosol-optical-depth (AOD) monthly means. In particular, the AODa/AOD ratio that varies within the (0.51–0.83) on autumn-winter (AW, October-March), varies within the (0.50–0.71) range on spring-summer (SS, April-September) as a consequence of the larger contribution of natural particles on SS. The surface (sfc), all-sky DRE by anthropogenic particles that is negative all year round at solar wavelengths, represents on average 60% and 51% of the all-sky sfc-DRE by all aerosols on AW and SS, respectively. The all-sky atmospheric forcing by anthropogenic particles (AFa) that is positive all year round, is little dependent on seasons: it varies within the (1.0–4.1)W/m2 and (2.0–4.2)W/m2 range on AW and SS, respectively. Conversely, the all-sky AF by all aerosols is characterized by a marked seasonality. As a consequence, the atmospheric forcing by anthropogenic particles that on average is 50% of the AF value on AW, decreases down to 36% of the AF value on SS. Infrared aerosol DREs that are positive all year round are significantly smaller than the corresponding absolute values of solar DREs. Clouds decrease on average ToA- and sfc-DRE absolute values by anthropogenic particles of 36% and 23%, respectively and are quite responsible of the seasonal dependence of aerosol forcing efficiencies by all and anthropogenic aerosols

Herança da resistência de variedades comerciais brasileiras de soja à podridão radicular de fitóftora.

O objetivo do estudo foi avaliar a herança da resistência à podridão radicular de fitóftora, causada por causada por Phytophthora sojae (Kaufm. & Gerd.), presentes em variedades comerciais resistentes BRS 260, BRS 262, BRS 246RR e BRSMG 752S. Até hoje 14 genes, denominados Rps, foram descritos por conferirem resistência à PRF, os quais tem sido amplamente utilizados nos programas de melhoramento para proteção das cultivares de soja. O material experimental foi desenvolvido a partir do cruzamento das quatro cultivares entre si, totalizando seis cruzamentos. A população F2, os parentais utilizados nos cruzamentos e a cultivar suscetível BRS 268, foram inoculados com o patógeno utilizando a metodologia de Keeling (1982), adaptada por Yorinori (1996). O teste do qui-quadrado (?2) foi aplicado para aceitar ou rejeitar os padrões de segregação encontrados de plantas mortas e não-mortas esperadas para a população F2 segundo padrões mendelianos. O cruzamento BRS 260 x BRS 246RR não resultou em nenhum indivíduo morto, com isso conclui-se que os mesmos contém um gene de resistência no mesmo loco conferindo resistência a P. sojae. Nos cruzamentos BRSMG 752S x BRS 260 e BRS 246RR x BRSMG 752S foram observados padrões de segregação semelhantes, correspondentes à segregação de dois genes dominantes independentes. As três combinações de cruzamentos envolvendo a cultivar BRS 262 indicam a presença de três genes segregando independentemente nesses cruzamentos. Pode-se concluir que apenas nesse grupo de quatro cultivares resistentes já existem quatro locos de resistência à P. sojae disponíveis para serem explorados em programas de melhoramento de soja

Mulheres atlânticas em movimento: o romance histórico pós-colonial de Ana Miranda e de José Eduardo Agualusa

This paper proposes a comparative study of Desmundo (1997) by the Brazilian Ana Miranda and Nação crioula (1997) by the Angolan José Eduardo Agualusa. The analysis focusses on the configuration of the protagonists of both novels. These protagonists transit the Atlantic Ocean which is characterized by symbolic exchanges and intense cultural contact: respectively a marriageable maiden who is compelled to immigrate to Brazil in order to strengthen the Lusitanian presence in the tropics, confirming the body of the white woman also as an instrument of European merchant machine, and a former slave and rich owner who becomes the embodiment of anti-abolitionist struggle in a mixed race Angola, confirming once again the body of the black woman as a slave trade merchandise.O artigo apresenta um estudo comparativo dos livros Desmundo (1997), da brasileira Ana Miranda, e Nação crioula (1997), do angolano José Eduardo Agualusa. O enfoque analítico incidirá sobre a configuração das personagens protagonistas, as quais transitam por um oceano Atlântico caracterizado por trocas simbólicas e trespasses culturais intensos: respectivamente, uma donzela casadoira que é compelida a imigrar para o Brasil, a fim de robustecer a presença lusitana nos trópicos, confirmando o corpo da mulher branca também como um instrumento da máquina mercante européia, e uma ex-escrava e rica proprietária que se torna a personificação da luta anti-abolicionista numa Angola mestiça, ratificando uma vez mais o corpo da mulher negra como mercadoria do tráfico negreiro

Biological Properties of IRIM, the Iridium(III) Analogue of (Imidazolium (Bisimidazole) Tetrachlororuthenate) (ICR)

Some biological aspects of the new complex imidazolium bisimidazole tetrachloro iridate(III)-IRIM- the iridium(III) analogue of ICR, were considered. More in detail the conformational effects produced by IRIM on DNA and the cytotoxic properties of IRIM on some selected human cell lines were measured. Dialysis experiments and DNA thermal denaturation studies are suggestive of poor binding of IRIM to DNA; formation of interstrand crosslinks is not observed. In any case CD measurements suggest that addition of increasing amounts of IRIM to calf thymus DNA results into significant spectral changes, that are diagnostic of a direct interaction with DNA. A number of experiments carried out on the A2780 human ovarian carcinoma, B16 murine melanoma, MCF7 and TS mammary adenocarcinoma tumor cell lines strongly point out that IRIM does not exhibit significant growth inhibition effects within the concentration range 10-4-10-6 M. It is suggested that the lower biological effects of IRIM compared to ICR are a consequence of the larger kinetic inertness of the iridium(III) center with respect to ruthenium(III)

monthly averaged anthropogenic aerosol direct radiative forcing over the mediterranean based on aeronet aerosol properties

Abstract. The all-sky direct radiative effect by anthropogenic aerosol (DREa) is calculated in the solar (0.3–4 μm) and infrared (4–200 μm) spectral ranges for six Mediterranean sites. The sites are differently affected by pollution and together reflect typical aerosol impacts that are expected over land and coastal sites of the central Mediterranean basin. Central to the simulations are aerosol optical properties from AERONET sun-/sky-photometer statistics for the year 2003. A discussion on the variability of the overall (natural + anthropogenic) aerosol properties with site location is provided. Supplementary data include MODIS satellite sensor based solar surface albedos, ISCCP products for high- mid- and low cloud cover and estimates for the anthropogenic aerosol fraction from global aerosol models. Since anthropogenic aerosol particles are considered to be smaller than 1 μm in size, mainly the solar radiation transfer is affected with impacts only during sun-light hours. At all sites the (daily average) solar DREa is negative all year round at the top of the atmosphere (ToA). Hence, anthropogenic particles produce over coastal and land sites of the central Mediterranean a significant cooling effect. Monthly DREa values vary from site to site and are seasonally dependent as a consequence of the seasonal dependence of available sun-light and microphysical aerosol properties. At the ToA the monthly average DREa is −(4±1) W m−2 during spring-summer (SS, April–September) and −(2±1) W m−2 during autumn-winter (AW, October–March) at the polluted sites. In contrast, it varies between −(3±1) W m−2 and −(1±1) W m−2 on SS and AW, respectively at the less polluted site. Due to atmospheric absorption the DREa at the surface is larger than at the ToA. At the surface the monthly average DREa varies between the most and the least polluted site between −(7±1) W m−2 and −(4±1) W m−2 during SS, and between −(4±3) W m−2 and −(1±1) W m−2 during AW. The DREa at infrared wavelengths is positive but negligible, especially at the ToA (<0.3 W m−2). The average of DREa monthly-means referring to all sites has allowed getting a ToA- and sfc-DREa yearly-mean value of −(3±2) and −(5±3) W m−2, respectively at solar wavelengths. Last data, even if refer to a particular year, indicate that the radiative energy-balance of Central Mediterranean land and coastal sites is quite affected by anthropogenic particles

Co-targeting of Bcl-2 and mTOR pathway triggers synergistic apoptosis in BH3 mimetics resistant acute lymphoblastic leukemia

Several chemo-resistance mechanisms including the Bcl-2 protein family overexpression and constitutive activation of the PI3K/Akt/mTOR signaling have been documented in acute lymphoblastic leukemia (ALL), encouraging targeted approaches to circumvent this clinical problem. Here we analyzed the activity of the BH3 mimetic ABT-737 in ALL, exploring the synergistic effects with the mTOR inhibitor CCI-779 on ABT-737 resistant cells. We showed that a low Mcl-1/Bcl-2 plus Bcl-xL protein ratio determined ABT-737 responsiveness. ABT-737 exposure further decreased Mcl-1, inducing apoptosis on sensitive models and primary samples, while not affecting resistant cells. Co-inhibition of Bcl-2 and the mTOR pathway resulted cytotoxic on ABT-737 resistant models, by downregulating mTORC1 activity and Mcl-1 in a proteasome-independent manner. Although Mcl-1 seemed to be critical, ectopic modulation did not correlate with apoptosis changes. Importantly, dual targeting proved effective on ABT-737 resistant samples, showing additive/synergistic effects. Together, our results show the efficacy of BH3 mimetics as single agent in the majority of the ALL samples and demonstrate that resistance to ABT-737 mostly correlated with Mcl-1 overexpression. Co-targeting of the Bcl-2 protein family and mTOR pathway enhanced drug-induced cytotoxicity by suppressing Mcl-1, providing a novel therapeutic approach to overcome BH3 mimetics resistance in ALL