ASSESSING EFFECTS TO ACQUATIC ORGANISMS OF CONTAMINANTS EXPOSURE ACROSS LEVELS OF BIOLOGICAL ORGANISATION, IN THE FRAME OF WFD 2000/60/EC

Gli ecosistemi acquatici sono il comparto ambientale finale per molti contaminanti introdotti nell’ambiente, specialmente per quelli persistenti, provenienti da diverse attività antropiche. Gli organismi acquatici sono esposti simultaneamente a differenti classi di composti chimici e, la loro fisiologia può esserne affetta anche da basse concentrazioni ambientali che ne determinano un effetto a cascata drammatico sull’intero ciclo vitale delle stesse. Per identificare gli effetti ecotossicologici si devono scegliere delle variabili di studio che sono sensibili a cambiamenti di esposizione e quindi possono registrare informazioni a differenti livelli di organizzazione biologica (ad es.: comunità, specie, alterazioni cellulari, molecolari). Il presente lavoro ha come scopo di studiare biomarker biochimici e bioindicatori su invertebrati acquatici capaci di rispondere all’effetto dei contaminanti e predirne il rischio di tossicità, requisito fondamentale dell’attuale legislazione comunitaria ambientale. Questo lavoro, nell’ambito della Water Frame Directive (WFD), affronta questa tematica con diversi tipi di approccio per implementare un sistema di monitorizzazione efficiente. Lo SPEAR ad esempio è in grado di diagnosticare la contaminazione di ecosistemi acquatici da pesticidi operando a livello di comunità di invertebrati acquatici. Inoltre si sono presi in considerazione anche biomarker a livello cellulare in bivalvi (Tapes philipphinarum and Mya arenaria): attività enzimatiche coinvolti nelle risposte aerobiche (CCO) e antiossidative (SOD and CAT), risposte genotossicologiche come la frequenza dei micronuclei, e, infine, a livello di organismo, risposte di carattere comportamentale.Aquatic ecosystems are the final sink for most of contaminants introduced in the environment, especially persistent organic pollutants coming from different human activities. Most of the freshwater and coastal organisms are exposed simultaneously to different classes of chemicals, and their physiology may be affected by toxic chemical even at low environmental concentrations with a cascade event on population dynamics. Identifying ecotoxicological effects requires descriptors that are sensitive to changes in exposure and thus can indicate information at different levels of biological organisation (i.e. communities, sub-individual level). The present work aims to investigate biochemical biomarkers and bioindicators in aquatic invertebrates able to detect biological effects and predict risk of toxicity, with a special focus paid to the requirements of current EU regulation. Therefore, the present work faced on different kinds of approach identified to be efficient tools within the context of the WFD requirements (Water Frame Directive, 2000/60/EC), for investigative and operational monitoring. Work include the SPEAR approach as trait based indicator descriptor of freshwater aquatic macroinvertebrates communities, able to diagnose pesticide contamination in aquatic ecosystems. Further diagnostic approaches in environmental status are included, as assay representing biological responses for different enzymes involved in the aerobic (CCO) and antioxidant responses, (SOD, and CAT), behavioural endpoints, and genotoxicity biomarker associated with micronuclei frequency in bivalve species (Tapes philipphinarum and Mya arenaria)

Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma

Quantification of HIV-1 proviral DNA in patients with undetectable plasma viremia over long-term highly active antiretroviral therapy

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An IL-15 dependent CD8 T cell response to selected HIV epitopes is related to viral control in early-treated HIV-infected subjects.

In some early-treated HIV+ patients, Structured Treatment Interruption (STI) is associated to spontaneous control of viral rebound. Thus, in this clinical setting, we analyzed the immunological parameters associated to viral control. Two groups of early treated patients who underwent STI were retrospectively defined, according to the ability to spontaneously control HIV replication (Controller and Non-controller). Plasma cytokine levels were analyzed by multiplex analysis. CD8 T cell differentiation was determined by polychromatic flow cytometry. Antigen-specific IFN-Γ production was analyzed by ELISpot and intracellular staining after stimulation with HIV-peptides. Long-term Elispot assays were performed in the presence or absence of IL-15. Plasma IL-15 was found decreased over a period of time in Non-Controller patients, whereas a restricted response to Gag (aa.167–202 and 265–279) and Nef (aa.86–100 and 111–138) immunodominant epitopes was more frequently observed in Controller patients. Interestingly, in two Non-Controller patients the CD8-mediated T cells response to immunodominant epitopes could be restored in vitro by IL-15, suggesting a major role of cytokine homeostasis on the generation of protective immunity. In early-treated HIV+ patients undergoing STI, HIV replication control was associated to CD8 T cell maturation and sustained IL-15 levels, leading to HIV-specific CD8 T cell responses against selected Gag and Nef epitopes

Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet.

Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery

Star Formation Histories of the LEGUS dwarf galaxies. II. Spatially resolved star formation history of the Magellanic irregular NGC 4449

We present a detailed study of the Magellanic irregular galaxy NGC 4449 based on both archival and new photometric data from the Legacy Extragalactic UV Survey, obtained with the Hubble Space Telescope Advanced Camera for Surveys and Wide Field Camera 3. Thanks to its proximity ($D=3.82\pm 0.27$ Mpc) we reach stars 3 magnitudes fainter than the tip of the red giant branch in the F814W filter. The recovered star formation history spans the whole Hubble time, but due to the age-metallicity degeneracy of the red giant branch stars, it is robust only over the lookback time reached by our photometry, i.e. $\sim 3$ Gyr. The most recent peak of star formation is around 10 Myr ago. The average surface density star formation rate over the whole galaxy lifetime is $0.01$ M$_{\odot}$ yr$^{-1}$ kpc$^{-2}$. From our study it emerges that NGC 4449 has experienced a fairly continuous star formation regime in the last 1 Gyr with peaks and dips whose star formation rates differ only by a factor of a few. The very complex and disturbed morphology of NGC 4449 makes it an interesting galaxy for studies of the relationship between interactions and starbursts, and our detailed and spatially resolved analysis of its star formation history does indeed provide some hints on the connection between these two phenomena in this peculiar dwarf galaxy.Comment: 16 pages, 25 figures. Accepted for publication in the Astrophysical Journa

Candidate LBV stars in galaxy NGC 7793 found via HST photometry + MUSE spectroscopy

Only about 19 Galactic and 25 extragalactic bonafide luminous blue variables (LBVs) are known to date. This incomplete census prevents our understanding of this crucial phase of massive star evolution which leads to the formation of heavy binary black holes via the classical channel. With large samples of LBVs one could better determine the duration and maximum stellar luminosity which characterize this phase. We search for candidate LBVs (cLBVs) in a new galaxy, NGC 7793. For this purpose, we combine high spatial resolution images from two Hubble Space Telescope (HST) programs with optical spectroscopy from the Multi Unit Spectroscopic Explorer (MUSE). By combining PSF-fitting photometry measured on F547M, F657N, and F814W images, with restrictions on point-like appearance (at HST resolution) and H α luminosity, we find 100 potential cLBVs, 36 of which fall in the MUSE fields. Five of the latter 36 sources are promising cLBVs which have MV ≤ −7 and a combination of: H α with a P-Cygni profile; no [O I]λ6300 emission; weak or no [O III]λ5007 emission; large [N II]/H α relative to H II regions; and [S II]λ6716/[S II]λ6731∼1⁠. It is not clear if these five cLBVs are isolated from O-type stars, which would favour the binary formation scenario of LBVs. Our study, which approximately covers one fourth of the optical disc of NGC 7793, demonstrates how by combining the above HST surveys with multi-object spectroscopy from 8-m class telescopes, one can efficiently find large samples of cLBVs in nearby galaxies

Neutrophil-lymphocyte ratio at diagnosis is an independent prognostic factor in patients with nodular sclerosis Hodgkin lymphoma: Results of a large multicenter study involving 990 patients

Several studies have demonstrated the prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with solid tumors and non-Hodgkin lymphoma. In contrast, there is only sparse data on its prognostic role in patients with classical Hodgkin lymphoma (cHL). The aim of our study was to establish whether NLR could serve as an independent prognostic factor in a cohort of 990 patients with nodular sclerosis (NS)-cHL. After analysis of the log hazard ratio (HR) as a function of NLR, we chose the value 6 as cutoff. Patients with NLR >6 had a worse progression-free survival and overall survival compared to those with NLR ≤6; 84% vs 75% and 92% vs 88%, at 5 years, with an HR of 1.65 and 1.82, respectively. Multivariate analysis showed that the risk remained high with HR 1.44 and HR 1.54 in progression-free survival and overall survival, respectively. In summary, our study shows that NLR is a robust and independent prognostic parameter in NS-cHL, both in early and advanced disease. It is inexpensive and simple to apply. Thus, we conclude that NLR, possibly in combination with the international prognostic score and absolute monocyte count, is a useful guide for physicians treating NS-cHL patients

An Open System for Social Computation

Part of the power of social computation comes from using the collective intelligence of humans to tame the aggregate uncertainty of (otherwise) low veracity data obtained from human and automated sources. We have witnessed a surge in development of social computing systems but, ironically, there have been few attempts to generalise across this activity so that creation of the underlying mechanisms themselves can be made more social. We describe a method for achieving this by standardising patterns of social computation via lightweight formal specifications (we call these social artifacts) that can be connected to existing internet architectures via a single model of computation. Upon this framework we build a mechanism for extracting provenance meta-data across social computations

Ecology of the facultative phytotelmic crab Platychirarma buettikoferi (De Man, 1883) (Decapoda, Brachyura, Sesarmidae)

The mangrove forests surrounding Douala, Cameroon, have a long history of human impact due to rapid urbanization, resulting in patches of true mangrove forest interspersed with areas dominated by the mangrove-associated Pandanus species. A survey carried out to assess the possible shift in crab fauna composition and dominance between mangrove and Pandanus dominated areas revealed an undescribed phytotelmic habitat for Platychirarma buettikoferi. This species was found colonizing the natural reservoirs of fresh water represented by Pandanus spp. Our results show P. buettikoferi to be ecologically dependent upon Pandanus spp., and absent on the mangrove floor and trees, strongly indicating a phytotelmic adaptation. Our data suggest that this species is a facultative phytotelmic species well adapted to Pandanus spp. dominated areas. Further studies on the reproductive biology and feeding behaviour of P. buettikoferi may shed light on this unique phytotelmic lifestyle and its role in mangrove ecosystem functioning