Structural Basis for Dityrosine-Mediated Inhibition of α-Synuclein Fibrillization

[Image: see text] α-Synuclein (α-Syn) is an intrinsically disordered protein which self-assembles into highly organized β-sheet structures that accumulate in plaques in brains of Parkinson’s disease patients. Oxidative stress influences α-Syn structure and self-assembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric α-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the α-Syn monomer by a factor of √2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation

Imaging of Flames in Cement Kilns To Study the Influence of Different Fuel Types

The cement industry aims to use an increased amount of alternative fuels to reduce production costs and CO₂ emissions. In this study three cement plants firing different kinds and percentages of alternative fuel were studied. A specially developed camera setup was used to monitor the flames in the three cement kilns and assess the effect of alternative fuels on the flame. It was found that cofiring with solid recovered fuel (SRF) would delay the ignition point by about 2 m and lower the intensity and temperature of the kiln flame compared to a fossil fuel flame. This is related to a larger particle size and moisture content of the alternative fuels, which lowers the conversion rate compared to fossil fuels. The consequences can be a lower kiln temperature and cement quality. The longer conversion time may also lead to the possibility of localized reducing conditions in the cement kiln, which can have a negative impact on the clinker quality and process stability. The burner design may alleviate some of the issues encountered with SRF cofiring. At one of the test plants the burner was changed from a design with an annular channel for axial air to a jet design. This proved to be beneficial for an early ignition and improved dispersion of the fuel and led to an increase in cement quality and higher use of SRF

UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Background The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis. Methodology/Principal Findings Here we report that cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed β-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality. Conclusions/Significance Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

The Bellinge data set: open data and models for community-wide urban drainage systems research

This paper describes a comprehensive and unique open-access data set for research within hydrological and hydraulic modelling of urban drainage systems. The data comes from a mainly combined urban drainage system covering a 1.7 km2 area in the town of Bellinge, a suburb to the city of Odense, Denmark. The data set consists of up to 10 years of observations (2010&ndash;2020) from 13 level meters, one flow meter, one position-sensor and four power sensors in the system, along with rainfall data from three rain gauges and two weather radars (X- and C-band), and meteorological data from a nearby weather station. The system characteristics of the urban drainage system (information about manholes, pipes etc.) can be found in the data set along with characteristics of the surface area (contour lines etc.). Two detailed hydrodynamic, distributed urban drainage models of the system are provided in the software systems Mike Urban and EPA SWMM. The two simulation models generally show similar responses, but systematic differences are present since the models have not been calibrated. With this data set we provide a useful case that enables independent testing and replication of results from future scientific developments and innovation within urban hydrology and urban drainage system research. The data set can be downloaded from https://doi.org/10.11583/DTU.c.5029124, (Pedersen et al., 2021a).&nbsp;</p