Hepatic DNA hydroxymethylation is site-specifically altered by chronic alcohol consumption and aging

Global DNA hydroxymethylation is markedly decreased in human cancers, including hepatocellular carcinoma, which is associated with chronic alcohol consumption and aging. Because gene-specific changes in hydroxymethylcytosine may affect gene transcription, giving rise to a carcinogenic environment, we determined genome-wide site-specific changes in hepatic hydroxymethylcytosine that are associated with chronic alcohol consumption and aging.Young (4 months) and old (18 months) male C57Bl/6 mice were fed either an ethanol-containing Lieber\u2013DeCarli liquid diet or an isocaloric control diet for 5 weeks. Genomic and gene-specific hydroxymethylcytosine patterns were determined through hydroxymethyl DNA immunoprecipitation array in hepatic DNA.Hydroxymethylcytosine patterns were more perturbed by alcohol consumption in young mice than in old mice (431 differentially hydroxymethylated regions, DhMRs, in young vs 189 DhMRs in old). A CpG island ~2.5 kb upstream of the glucocorticoid receptor gene, Nr3c1, had increased hydroxymethylation as well as increased mRNA expression (p = 0.015) in young mice fed alcohol relative to the control group. Aging alone also altered hydroxymethylcytosine patterns, with 331 DhMRs, but alcohol attenuated this effect. Aging was associated with a decrease in hydroxymethylcytosine ~1 kb upstream of the leptin receptor gene, Lepr, and decreased transcription of this gene (p = 0.029). Nr3c1 and Lepr are both involved in hepatic lipid homeostasis and hepatosteatosis, which may create a carcinogenic environment. These results suggest that the location of hydroxymethylcytosine in the genome is site specific and not random, and that changes in hydroxymethylation may play a role in the liver\u2019s response to aging and alcohol

Encouraging results for controlling an Agricultural pest on St. Eustatius

In 2013, the invasive Giant African Land Snail, Achatina fulica was found in a small part of urban St. Eustatius. In collaboration with local government agencies and Dutch universities, IMARES* conducted field and laboratory pilot trials of control methods from October 2015 to June 2016

A novel 10B-enriched carboranyl-containing phthalocyanine as a radio- and photo-sensitising agent for boron neutron capture therapy and photodynamic therapy of tumours: in vitro and in vivo studies

The synthesis of a Zn(II)-phthalocyanine derivative bearing four B-10-enriched o-carboranyl units (B-10-ZnB4Pc) and its natural isotopic abundance analogue (ZnB4Pc) in the peripheral positions of the tetraazaisoindole macrocycle is presented. The photophysical properties of ZnB4Pc, as tested against model biological systems, were found to be similar with those typical of other photodynamically active porphyrin-type photosensitisers, including a singlet oxygen quantum yield of 0.67. The carboranyl-carrying phthalocyanine was efficiently accumulated by B16F1 melanotic melanoma cells in vitro, appeared to be partitioned in at least some subcellular organelles and, upon red light irradiation, induced extensive cell mortality. Moreover, ZnB4Pc, once i.v.-injected to C57BL/6 mice bearing a subcutaneously transplanted pigmented melanoma, photosensitised an important tumour response, provided that the irradiation at 600-700 nm was performed 3 h after the phthalocyanine administration, when appreciable concentrations of ZnB4Pc were still present in the serum. Analogously, irradiation of the B-10-ZnB4Pc-loaded pigmented melanoma with thermal neutrons 24 h after injection led to a 4 day delay in tumour growth as compared with control untreated mice. These results open the possibility to use one chemical compound as both a photosensitising and a radiosensitising agent for the treatment of tumours by the combined application of photodynamic therapy and boron neutron capture therapy

Tumour-localizing and -photo sensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)

A water-soluble meso-substituted porphyrin (H2TCP) bearing 36 boron atoms, which appeared to be an efficient photodynamic sensitiser (singlet oxygen quantum yield=0.44), was studied for its accumulation by murine melanotic melanoma cells (B16F1). The amount of H2TCP in the cells increased with the porphyrin dose in the incubation medium up to, and at least, 100 mu M concentrations with no significant cytotoxic effect in the dark. Moreover, the H2TCP uptake increased with the incubation time reaching a plateau value corresponding with the recovery of 0.4 nmol of H2TCP per mg of cell proteins after 24 h incubation. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly, exhibiting a discrete distribution in the cytoplasm with a pattern which was closely similar to that observed for the endosomal probe Lucifer yellow. The photosensitising efficiency of the H2TCP toward B16F1 cells was studied for different irradiation (1-15 min) and incubation (1-24 h) times. Nearly complete (> 95%) cell mortality was obtained upon incubation with 20 mu M H2TCP and 10 min irradiation with red light (600-700 nm, 20 mW/cm(2)). The porphyrin was also accumulated in appreciable amounts by the tumour tissue after intravenous injection to C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma. Maximum accumulation in the turnout was achieved by administration of H2TCP dissolved in the ternary mixture 20% dimethylsulfoxide (DMSO)-30% polyethyleneglycol (PEG 400)-50% water. Thus, this porphyrin could act as both a photodynamic therapy agent and a radiosensitising agent for boron neutron capture therapy

The JANUS camera onboard JUICE mission for Jupiter system optical imaging

JANUS (Jovis, Amorum ac Natorum Undique Scrutator) is the visible camera selected for the ESA JUICE mission to the Jupiter system. Resources constraints, S/C characteristics, mission design, environment and the great variability of observing conditions for several targets put stringent constraints on instrument architecture. In addition to the usual requirements for a planetary mission, the problem of mass and power consumption is particularly stringent due to the long-lasting cruising and operations at large distance from the Sun. JANUS design shall cope with a wide range of targets, from Jupiter atmosphere, to solid satellite surfaces, exosphere, rings, and lightning, all to be observed in several color and narrow-band filters. All targets shall be tracked during the mission and in some specific cases the DTM will be derived from stereo imaging. Mission design allows a quite long time range for observations in Jupiter system, with orbits around Jupiter and multiple fly-bys of satellites for 2.5 years, followed by about 6 months in orbit around Ganymede, at surface distances variable from 104 to few hundreds km. Our concept was based on a single optical channel, which was fine-tuned to cover all scientific objectives based on low to high-resolution imaging. A catoptric telescope with excellent optical quality is coupled with a rectangular detector, avoiding any scanning mechanism. In this paper the present JANUS design and its foreseen scientific capabilities are discussed

Tumour-localizing and -photosensitising properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H\u3csub\u3e2\u3c/sub\u3eTCP)

A water-soluble meso-substituted porphyrin (H2TCP) bearing 36 boron atoms, which appeared to be an efficient photodynamic sensitiser (singlet oxygen quantum yield = 0.44), was studied for its accumulation by murine melanotic melanoma cells (B16F1). The amount of H2TCP in the cells increased with the porphyrin dose in the incubation medium up to, and at least, 100 μM concentrations with no significant cytotoxic effect in the dark. Moreover, the H2TCP uptake increased with the incubation time reaching a plateau value corresponding with the recovery of 0.4 nmol of H2TCP per mg of cell proteins after 24 h incubation. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly, exhibiting a discrete distribution in the cytoplasm with a pattern which was closely similar to that observed for the endosomal probe Lucifer yellow. The photosensitising efficiency of the H2TCP toward B16F1 cells was studied for different irradiation (1-15 min) and incubation (1-24 h) times. Nearly complete (\u3e95%) cell mortality was obtained upon incubation with 20 μM H2TCP and 10 min irradiation with red light (600-700 nm, 20 mW/cm2). The porphyrin was also accumulated in appreciable amounts by the tumour tissue after intravenous injection to C57BL/6 mice bearing a subcutaneously transplanted melanotic melanoma. Maximum accumulation in the tumour was achieved by administration of H2TCP dissolved in the ternary mixture 20% dimethylsulfoxide (DMSO)-30% polyethyleneglycol (PEG 400)-50% water. Thus, this porphyrin could act as both a photodynamic therapy agent and a radiosensitising agent for boron neutron capture therapy. © 2007 Elsevier B.V. All rights reserved

Optical design and stray light analysis for the JANUS camera of the JUICE space mission

The JUICE (JUpiter ICy moons Explorer) satellite of the European Space Agency (ESA) is dedicated to the detailed study of Jupiter and its moons. Among the whole instrument suite, JANUS (Jovis, Amorum ac Natorum Undique Scrutator) is the camera system of JUICE designed for imaging at visible wavelengths. It will conduct an in-depth study of Ganymede, Callisto and Europa, and explore most of the Jovian system and Jupiter itself, performing, in the case of Ganymede, a global mapping of the satellite with a resolution of 400 m/px. The optical design chosen to meet the scientific goals of JANUS is a three mirror anastigmatic system in an off-axis configuration. To ensure that the achieved contrast is high enough to observe the features on the surface of the satellites, we also performed a preliminary stray light analysis of the telescope. We provide here a short description of the optical design and we present the procedure adopted to evaluate the stray-light expected during the mapping phase of the surface of Ganymede. We also use the results obtained from the first run of simulations to optimize the baffle design

Treatment with COLchicine in hospitalized patients affected by COVID-19: The COLVID-19 trial

Objective: To evaluate whether the addition of colchicine to standard of care (SOC) results in better outcomes in hospitalized patients with COVID-19. Design: This interventional, multicenter, randomized, phase 2 study, evaluated colchicine 1.5 mg/day added to SOC in hospitalized COVID-19 patients (COLVID-19 trial) and 227 patients were recruited. The primary outcome was the rate of critical disease in 30 days defined as need of mechanical ventilation, intensive care unit (ICU), or death. Results: 152 non-anti-SARS-CoV-2-vaccinated patients (colchicine vs controls: 77vs75, mean age 69.1±13.1 vs 67.9±15 years, 39% vs 33.3% females, respectively) were analyzed. There was no difference in co-primary end-points between patients treated with colchicine compared to controls (mechanical ventilation 5.2% vs 4%, ICU 1.3% vs 5.3%, death 9.1% vs 6.7%, overall 11 (14.3%) vs 10 (13.3%) patients, P=ns, respectively). Mean time to discharge was similar (colchicine vs controls 14.1±10.4 vs 14.7±8.1 days). Older age (>60 years, P=0.025), P/F40 U/L (P<0.001), pre-existent heart (P=0.02), lung (P=0.003), upper-gastrointestinal (P=0.014), lower-gastrointestinal diseases (P=0.009) and cancer (P=0.008) were predictive of achieving the primary outcome. Diarrhoea (9.1% vs 0%, p=0.0031) and increased levels of AST at 6 days (76.9±91.8 vs 33.5±20.7 U/l, P=0.016) were more frequent in the colchicine group. Conclusion: Colchicine did not reduce the rate and the time to the critical stage. Colchicine was relatively safe although adverse hepatic effects require caution. We confirm that older (>60 years) patients with comorbidities are characterized by worse outcome