Prochloraz is widely used in horticulture and agriculture, e.g. as a post-harvest anti-mold treatment. Prochloraz is a known endocrine disruptor causing developmental toxicity with multiple ...mechanisms of action. However, data are scarce concerning other toxic effects. Since oxidative stress response, with formation of reactive oxygen species (ROS), is a common mechanism for different toxic endpoints, e.g. genotoxicity, carcinogenicity and teratogenicity, the aim of this study was to investigate if prochloraz can induce oxidative stress and/or DNA damage in human cells. A cell culture based in vitro model was used to study oxidative stress response by prochloraz, as measured by the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), a key molecule in oxidative defense mechanisms. It was observed that prochloraz induced oxidative stress in cultured human adrenocortical H295R and hepatoma HepG2 cells at non-toxic concentrations. Further, we used Comet assay to investigate the DNA damaging potential of prochloraz, and found that non-toxic concentrations of prochloraz induced DNA damage in HepG2 cells. These are novel findings, contradicting previous studies in the field of prochloraz and genotoxicity. This study reports a new mechanism by which prochloraz may exert toxicity. Our findings suggest that prochloraz might have genotoxic properties.
•Prochloraz induces oxidative stress-related Nrf2 activity in cultured human cells.•Prochloraz induces DNA damage in cultured human cells.•These findings suggest that prochloraz might have genotoxic properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mastitis is the most common disease in dairy herds worldwide and is often caused by Staphylococcus aureus. Little is known about the effect of mastitis on transporters in the mammary gland and the ...effect on transporter-mediated secretion of drugs into milk. We studied gene expressions of ATP-binding cassette and solute carrier transporters in S. aureus-infected mammary glands of mice. On d 7 of lactation, NMRI mice were inoculated with 1,000 cfu of S. aureus in 2 mammary glands and with a saline vehicle in 2 control glands. Gene expression of the transporters, Bcrp, Mdr1, Mrp1, Oatp1a5, Octn1, and Oct1, and of Csn2, the gene encoding β-casein, were determined in mammary glands at 72 h after treatment. As biomarkers of the inflammatory response gene, expressions of the cytokines Il6, Tnfα, and the chemokine Cxcl2 were measured. Despite a high individual variation between the 6 animals, some characteristic patterns were evident. The 3 inflammatory biomarkers were upregulated in all animals; Csn2 was downregulated compared with controls in all animals, although not statistically significantly. Both Mrp1 and Oatp1a5 were statistically significantly upregulated and Bcrp was downregulated. Gene expression of Bcrp followed the expression of Csn2 in each of the animals, indicating a possible co-regulation. The findings demonstrate that S. aureus infection has an effect on expression of drug transporters in the mammary gland, which may affect secretion of drugs into milk and efficacy of drug therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The HIBEAM/NNBAR Calorimeter Prototype Dunne, K; Meirose, B; Milstead, D ...
Journal of physics. Conference series,
11/2022, Volume:
2374, Issue:
1
Journal Article
Peer reviewed
Open access
The HIBEAM/NNBAR experiment is a free-neutron search for
n
→ sterile
n
and
n
→
n
¯
oscillations planned to be installed at the European Spallation Source under construction in Lund, Sweden. A key ...component in the experiment is the detector to identify
n
–
n
¯
annihilation events, which will produce on average four pions with a final state invariant mass of two nucleons, around 1.9 GeV. The beamline and experiment are shielded from magnetic fields which would suppress
n
→
n
¯
transitions, thus no momentum measurement will be possible. Additionally, calorimetry for particles with kinetic energies below 600 MeV is challenging, as traditional sampling calorimeters used in HEP would suffer from poor shower statistics. A design study is underway to use a novel approach of a hadronic range measurement in multiple plastic scintillator layers, followed by EM calorimetery with lead glass. A prototype calorimeter system is being built, and will eventually be installed at an ESS test beam line for
in situ
neutron background studies.
The NNBAR experiment for the European Spallation Source will search for free neutrons converting to antineutrons with an expected sensitivity improvement of three orders of magnitude compared to the ...last such search. This paper describes both the simulations of a key component for the experiment, the neutron optical reflector and the expected gains in sensitivity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
5.
QCD challenges from pp to A–A collisions Adolfsson, J.; Andronic, A.; Bierlich, C. ...
The European physical journal. A, Hadrons and nuclei,
2020, Volume:
56, Issue:
11
Journal Article
Peer reviewed
Open access
This paper is a write-up of the ideas that were presented, developed and discussed at the third International Workshop on QCD Challenges from pp to A–A, which took place in August 2019 in Lund, ...Sweden (Workshop link:
https://indico.lucas.lu.se/event/1214/
). The goal of the workshop was to focus on some of the open questions in the field and try to come up with concrete suggestions for how to make progress on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This paper presents the test results of the second prototype of SAMPA, the ASIC designed for the upgrade of read-out front end electronics of the ALICE Time Projection Chamber (TPC) and Muon Chamber ...(MCH). SAMPA is made in a 130 nm CMOS technology with 1.25 V nominal voltage supply and provides 32 channels, with selectable input polarity, and three possible combinations of shaping time and sensitivity. Each channel consists of a Charge Sensitive Amplifier, a semi-Gaussian shaper and a 10-bit ADC; a Digital Signal Processor provides digital filtering and compression capability. In the second prototype run both full chip and single test blocks were fabricated, allowing block characterization and full system behaviour studies. Experimental results are here presented showing agreement with requirements for both the blocks and the full chip.
A high resolution TPC is the main option for a central tracking detector at the future International Linear Collider (ILC). It is planned that the MPGD (Micro Pattern Gas Detector) technology will be ...used for the readout. A Large Prototype TPC at DESY has been used to test the performance of MPGDs in an electron beam of energies up to 6 GeV. The first step in the technology development was to demonstrate that the MPGDs are able to achieve the necessary performance set by the goals of ILC. For this 'proof of principle' phase, the ALTRO front-end electronics from the ALICE TPC was used, modified to adapt to MPGD readout. The proof of principle has been verified and at present further improvement of the MPGD technology is going on, using the same readout electronics. The next step is the 'feasibility phase', which aims at producing front-end electronics comparable in size (few mm super(2)) to the readout pads of the TPC. This development work is based on the succeeding SALTRO16 chip, which combines the analogue and digital signal processing in the same chip. This paper summarizes the status of this work and discusses how the experiences made so far can be exploited to improve the final readout electronics.
Alcohol consumption and increased estrogen levels are major risk factors for breast cancer, and peroxisome proliferator-activated receptor γ (PPAR-γ) plays an important role in alcohol-induced breast ...cancer. PPAR-γ activity is inhibited by ethanol, leading to increased aromatase activity and estrogen biosynthesis ultimately leading to breast cancer. If other organic solvents inhibit PPAR-γ activity, they should also lead to increased oestrogen biosynthesis and thus be potential breast carcinogens. Ten commonly used hydrophilic organic solvents were first tested in a cell-based screening assay for inhibitory effects on PPAR-γ transactivation. The chemicals shown to inhibit PPAR-γ were tested with vectors encoding PPAR-γ with deleted AB domains and only the ligand-binding domain to rule out unspecific toxicity. Next, the effects on biosynthesis of estradiol, testosterone and oestrone sulphate were measured in the H295R steroidogenesis assay after incubation with the chemicals. Ethylene glycol, ethyl acetate, and dimethyl sulphoxide inhibited PPAR-γ transactivation in a dose-dependent manner. The inhibitory effect on PPAR-γ was specific for PPAR-γ since the AB domain of PPAR-γ was required for the inhibitory effect. In the second step, ethylene glycol significantly increased production of oestradiol by 19% (p < 0.05) and ethyl acetate inhibited production of testosterone (p < 0.05). We here show that screening of 10 commonly used organic solvents for the ability to inhibit PPAR-γ transactivation followed by a well-established steroidogenesis assay for production of sex hormones in exposed H295 R cells may provide a screening tool for potential breast carcinogens. This initial screening thus identified ethylene glycol and possibly ethyl acetate as potential breast carcinogens.
Alcohol consumption and increased estrogen levels are major risk factors for breast cancer, and peroxisome proliferator-activated receptor γ (PPAR-γ) plays an important role in alcohol-induced breast ...cancer. PPAR-γ activity is inhibited by ethanol, leading to increased aromatase activity and estrogen biosynthesis ultimately leading to breast cancer. If other organic solvents inhibit PPAR-γ activity, they should also lead to increased oestrogen biosynthesis and thus be potential breast carcinogens. Ten commonly used hydrophilic organic solvents were first tested in a cell-based screening assay for inhibitory effects on PPAR-γ transactivation. The chemicals shown to inhibit PPAR-γ were tested with vectors encoding PPAR-γ with deleted AB domains and only the ligand-binding domain to rule out unspecific toxicity. Next, the effects on biosynthesis of estradiol, testosterone and oestrone sulphate were measured in the H295R steroidogenesis assay after incubation with the chemicals. Ethylene glycol, ethyl acetate, and dimethyl sulphoxide inhibited PPAR-γ transactivation in a dose-dependent manner. The inhibitory effect on PPAR-γ was specific for PPAR-γ since the AB domain of PPAR-γ was required for the inhibitory effect. In the second step, ethylene glycol significantly increased production of oestradiol by 19% (p < 0.05) and ethyl acetate inhibited production of testosterone (p < 0.05). We here show that screening of 10 commonly used organic solvents for the ability to inhibit PPAR-γ transactivation followed by a well-established steroidogenesis assay for production of sex hormones in exposed H295 R cells may provide a screening tool for potential breast carcinogens. This initial screening thus identified ethylene glycol and possibly ethyl acetate as potential breast carcinogens.
Prader-Willi syndrome (PWS) is a rare genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioral challenges, cognitive dysfunction, and hormone deficiencies. ...Hypogonadism is common but knowledge on potential side effects of testosterone replacement is limited, in particular, the long-term effects on behavior and PSA.
Retrospective case studies of seven men, median age 46 years, with genetically verified PWS, testosterone treated hypogonadism and available PSA values were included. Long-term follow-up of PSA was accessible in four patients. Medical records were reviewed for adverse effects.
Five men were treated with intramuscular testosterone undecanoate, two had no hypogonadism. Median PSA was 0.68 μg/L (0.23–1.3), median testosterone 15 nmol/L. After a median time of 17 years of testosterone replacement median PSA was 0.75 μg/L (range 0.46–1.4). Testosterone replacement was well tolerated, and no major behavioral changes were reported. Five were treated with growth hormone for >20 years.
Levels of PSA were low. Long-term treatment with testosterone was working well and did not result in any clinically meaningful increase in PSA. Our results indicate that testosterone replacement is neither associated with serious adverse events regarding changes in behavior or effect on PSA. However, larger studies are needed to confirm our results.
•This case series of seven men with Prader-Willi syndrome showed:•Levels of prostate specific antigen (PSA) were low•Long-term testosterone treatment had no or limited effect on PSA•Long-term testosterone treatment was well tolerated•Awaiting more data, regular monitoring of PSA during testosterone treatment is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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