Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2

An experimentally determined structure for human CYP2J2—a member of the cytochrome P450 family with significant and diverse roles across a number of tissues—does not yet exist. Our understanding of how CYP2J2 accommodates its cognate substrates and how it might be inhibited by other ligands thus relies on our ability to computationally predict such interactions using modelling techniques. In this study we present a computational investigation of the binding of arachidonic acid (AA) to CYP2J2 using homology modelling, induced fit docking (IFD) and molecular dynamics (MD) simulations. Our study reveals a catalytically competent binding mode for AA that is distinct from a recently published study that followed a different computational pipeline. Our proposed binding mode for AA is supported by crystal structures of complexes of related enzymes to inhibitors, and evolutionary conservation of a residue whose role appears essential for placing AA in the right site for catalysis

\u27Joo wa dare?\u27 Who is the Queen? Queen Contests During the Wartime Incarceration of Japanese Americans

This paper examines beauty pageants held at incarceration centers during the Japanese-American internment. Although there has been literature created on beauty pageants before and after WWII, there is very little information on these war-era pageants, despite their prolific nature. Using mostly primary sources and material culture, the paper examines the coverage of the contestants, clothing, and presentation within the Center’s newspapers and in coverage by the Wartime Relocation Authority, whilst also problematizing uncritical readings of these documents. This paper highlights the difficulty in determining agency within spaces of incarceration, and calls for further research on the subject

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

Predicting language diversity with complex network

Evolution and propagation of the world's languages is a complex phenomenon, driven, to a large extent, by social interactions. Multilingual society can be seen as a system of interacting agents, where the interaction leads to a modification of the language spoken by the individuals. Two people can reach the state of full linguistic compatibility due to the positive interactions, like transfer of loanwords. But, on the other hand, if they speak entirely different languages, they will separate from each other. These simple observations make the network science the most suitable framework to describe and analyze dynamics of language change. Although many mechanisms have been explained, we lack a qualitative description of the scaling behavior for different sizes of a population. Here we address the issue of the language diversity in societies of different sizes, and we show that local interactions are crucial to capture characteristics of the empirical data. We propose a model of social interactions, extending the idea from, that explains the growth of the language diversity with the size of a population of country or society. We argue that high clustering and network disintegration are the most important characteristics of models properly describing empirical data. Furthermore, we cancel the contradiction between previous models and the Solomon Islands case. Our results demonstrate the importance of the topology of the network, and the rewiring mechanism in the process of language change

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Transgender identity in young people and adults recorded in UK primary care electronic patient records: retrospective, dynamic, cohort study

OBJECTIVES: To quantify the change in proportion of young people and adults identified as transgender in UK primary care records and to explore whether rates differ by age and socioeconomic deprivation. DESIGN: Retrospective, dynamic, cohort study. SETTING: IQVIA Medical Research Data, a database of electronic primary care records capturing data from 649 primary care practices in the UK between 1 January 2000 and 31 December 2018. PARTICIPANTS: 7 064 829 individuals aged 10-99 years, in all four UK countries. MAIN OUTCOME MEASURES: Diagnostic codes indicative of transgender identity were used. Sex assigned at birth was estimated by use of masculinising or feminising medication and procedural/diagnostic codes. RESULTS: 2462 (0.03%) individuals had a record code indicating a transgender identity. Direction of transition could be estimated for 1340 (54%) people, of which 923 were assigned male at birth, and 417 were assigned female at birth. Rates of recording in age groups diverged substantially after 2010. Rates of the first recording of codes were highest in ages 16-17 years (between 2010 and 2018: 24.51/100 000 person years (95% confidence interval 20.95 to 28.50)). Transgender codes were associated with deprivation: the rate of the first recording was 1.59 (95% confidence interval 1.31 to 1.92) in the most deprived group in comparison with the least deprived group. Additionally, the rate ratio of the proportion of people who identified as transgender was 2.45 (95% confidence interval 2.28 to 2.65) in the most deprived group compared with the least deprived group. Substantial increases were noted in newly recorded transgender codes over time in all age groups (1.45/100 000 person years in 2000 (95% confidence interval 0.96 to 2.10) to 7.81/100 000 person years in 2018 (6.57 to 9.22)). In 2018, the proportion of people with transgender identity codes was highest in the age groups 16-17 years (16.23 per 10 000 (95% confidence interval 12.60 to 20.57)) and 18-29 years (12.42 per 10 000 (11.06 to 13.90)). CONCLUSION: The rate of transgender identity recorded in primary care records has increased fivefold from 2000 to 2018 and is highest in the 16-17 and 18-29 age groups. Transgender diagnostic coding is associated with socioeconomic deprivation and further work should investigate this association. Primary and specialist care should be commissioned accordingly to provide for the gender specific and general health needs of transgender people

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Size constancy is preserved but afterimages are prolonged in typical individuals with higher degrees of self-reported autistic traits

Deficits in perceptual constancies from early infancy have been proposed to contribute to autism and exacerbate its symptoms (Hellendoorn et al., Frontiers in Psychology 6:1–16, 2015). Here, we examined size constancy in adults from the general population (N = 106) with different levels of self-reported autistic traits using an approach based on negative afterimages. The afterimage strength, as indexed by duration and vividness, was also quantified. In opposition to the Hellendoorn and colleagues’ model, we were unable to demonstrate any kind of relationship between abilities in size constancy and autistic traits. However, our results demonstrated that individuals with higher degrees of autistic traits experienced more persistent afterimages. We discuss possible retinal and post-retinal explanations for prolonged afterimages in people with higher levels of autistic traits

Molecular dynamics simulations of the interaction of wild type and mutant human CYP2J2 with polyunsaturated fatty acids

Objectives: The data presented here is part of a study that was aimed at characterizing the molecular mechanisms of polyunsaturated fatty acid metabolism by CYP2J2, the main cytochrome P450 enzyme active in the human cardiovasculature. This part comprises the molecular dynamics simulations of the binding of three eicosanoid substrates to wild type and mutant forms of the enzyme. These simulations were carried out with the aim of dissecting the importance of individual residues in the active site and the roles they might play in dictating the binding and catalytic specificity exhibited by CYP2J2. Data description: The data comprise: a) a new homology model of CYP2J2, b) a number of predicted low-energy complexes of CYP2J2 with arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, produced with molecular docking and c) a series of molecular dynamics simulations of the wild type and four mutants interacting with arachidonic acid as well as simulations of the wild type interacting with the two other eicosanoid ligands. The simulations may be helpful in identifying the determinants of substrate specificity of this enzyme and in unraveling the role of individual mutations on its function. They may also help guide the generation of mutants with altered substrate preferences