| 1. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 2. |
- Lewin, Erik, et al.
(författare)
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Industrialisation Study of Nanocomposite nc-TiC/a-C Coatings for Electrical Contact Applications
- 2009
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Ingår i: Plasma Processes and Polymers. - : WILEY-VCH Verlag GmbH & Co. - 1612-8850. ; 6:S1, s. S928-S934
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Tidskriftsartikel (refereegranskat)abstract
- Nanocomposite nc-TiC/a-C coatings were prepared by non-reactive magnetron sputtering in industrial scale equipment, under varying deposition conditions in order to investigate upscaling and possible industrialisation. The coatings were found to have similar microstructure and performance compared to previous laboratory scale experiments. The samples were characterised with XRD, XPS and SEM as well with ball-on-disc, nanoindentation and electrical measurements. Coatings containing a small fraction of a-C matrix phase were found to have promising both electrical properties (rho < 400 mu Omega cm and contact resistances down to 0.34 m Omega at 40 N) and tribological properties (f < 0.3 for 10 000 laps).
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| 3. |
- Gustafsson, Sofia B, et al.
(författare)
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High tumour cannabinoid CB(1) receptor immunoreactivity negatively impacts disease-specific survival in stage II microsatellite stable colorectal cancer
- 2011
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Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science. - 1932-6203. ; 6:8, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. Methodology/Principal Findings: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and >= 2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB1IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 8565 and 66+/-8%; tumour interior, 86+/-4% and 63+/-8% for the CB(1)IR<2 and CB(1)IR >= 2 groups, respectively. Conclusions/Significance: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients.
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| 4. |
- Lind, Lars, et al.
(författare)
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Uppsala Consensus Statement on Environmental Contaminants and the Global Obesity Epidemic
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:5, s. A81-A83
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Tidskriftsartikel (refereegranskat)abstract
- From the lectures presented at the 2nd International Workshop on Obesity and Environmental Contaminants, which was held in Uppsala, Sweden, on 8–9 October 2015, it became evident that the findings from numerous animal and epidemiological studies are consistent with the hypothesis that environmental contaminants could contribute to the global obesity epidemic. To increase awareness of this important issue among scientists, regulatory agencies, politicians, chemical industry management, and the general public, the authors summarize compelling scientific evidence that supports the hypothesis and discuss actions that could restrict the possible harmful effects of environmental contaminants on obesity.
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| 5. |
- Miller, Daniel J., et al.
(författare)
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Low O-2 dissociation barrier on Pt(111) due to adsorbate-adsorbate interactions
- 2010
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Ingår i: Journal of Chemical Physics. - : American Institute of Physics. - 0021-9606 .- 1089-7690. ; 133:22, s. 224701-
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Tidskriftsartikel (refereegranskat)abstract
- O2 dissociation on Pt(111) has been followed at low and saturation coverage using temperature-programmed x-ray photoelectron spectroscopy and simulated with mean-field kinetic modeling, yielding dissociation (Ea) and desorption (Ed) barriers of 0.32 and 0.36 eV, respectively. DFT calculations show that Ea is strongly influenced by the O–O interatomic potential in the atomic final state: of the supercells considered, that which maximizes attractive third-nearest-neighbor interactions in the atomic final state yields both the lowest computed dissociation barrier (0.24 eV) and the best agreement with experiment. It is proposed that the effect of adsorbate-adsorbate interactions must be considered when modeling catalytic processes involving dissociative steps.
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| 6. |
- Drakvik, E., et al.
(författare)
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Statement on advancing the assessment of chemical mixtures and their risks for human health and the environment
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: • We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. • Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. • Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. • A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient. © 2019 The Authors
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| 7. |
- Isaksson-Mettävainio, Martin, et al.
(författare)
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High SMAD4 levels appear in MSI and hypermethylated colon cancers, and indicate a better prognosis
- 2012
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 131, s. 779-788
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is one of the most common causes of cancer related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. 479 paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 expression, on the other hand, was significantly associated with increased survival, especially in colon cancer patients which has undergone potential curative surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression was significantly related to increase in survival, while loss of SMAD4 resulted in a significantly poorer prognosis. SMAD4 expression was not correlated to prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor prognosis in colon cancer patients. The novel findings that high SMAD4 expression predicts a better prognosis suggests that SMAD4 immunohistochemistry could constitute a prognostic marker in combination with CIMP and MSI screening status.
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| 8. |
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