Changes in the luminescence of poly(ethylene terephthalate) (PET) degraded in the absence and presence of oxygen at melt temperatures has been investigated. On oxidative degradation monomer ...fluorescence is reduced, with a concurrent increase in dimer fluorescence at long wavelengths. This is consistent with main chain breakdown and aggregation of the terephthalate fragments produced. Longer wavelength fluorescent species have been assigned to hydroxylation of the aromatic rings of PET. Further oxidation of PET degraded in air elicits changes in fluorescence and phosphorescence which have been associated with oxidation of hydroxylated units which exist in equilibrium with quinones by a redox mechanism. Phosphorescence studies on extracts from heavily oxidized PET have indicated the presence of stilbene quinone type impurities. The absence of such changes in the luminescence of PET degraded in nitrogen indicates hydroxylated, quinone and stilbene quinone species arise primarily from oxidation reactions. These species are suggested to contribute to the yellowing of PET on degradation.
The ASTRODEEP Frontier Fields catalogues Di Criscienzo, M.; Merlin, E.; Castellano, M. ...
Astronomy and astrophysics (Berlin),
11/2017, Volume:
607
Journal Article
Abstract
STUDY QUESTION
Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins?
SUMMARY ANSWER
We identified four new loci, GNRH1, FSHR, ZFPM1, and ...IPO8, in addition to previously identified loci, FSHB and SMAD3.
WHAT IS KNOWN ALREADY
The propensity to give birth to DZ twins runs in families. Earlier, we reported that FSHB and SMAD3 as associated with DZ twinning and female fertility measures.
STUDY DESIGN, SIZE, DURATION
We conducted a genome-wide association meta-analysis (GWAMA) of mothers of spontaneous dizygotic (DZ) twins (8265 cases, 264 567 controls) and of independent DZ twin offspring (26 252 cases, 417 433 controls).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Over 700 000 mothers of DZ twins, twin individuals and singletons from large cohorts in Australia/New Zealand, Europe, and the USA were carefully screened to exclude twins born after use of ARTs. Genetic association analyses by cohort were followed by meta-analysis, phenome wide association studies (PheWAS), in silico and in vivo annotations, and Zebrafish functional validation.
MAIN RESULTS AND THE ROLE OF CHANCE
This study enlarges the sample size considerably from previous efforts, finding four genome-wide significant loci, including two novel signals and a further two novel genes that are implicated by gene level enrichment analyses. The novel loci, GNRH1 and FSHR, have well-established roles in female reproduction whereas ZFPM1 and IPO8 have not previously been implicated in female fertility. We found significant genetic correlations with multiple aspects of female reproduction and body size as well as evidence for significant selection against DZ twinning during human evolution. The 26 top single nucleotide polymorphisms (SNPs) from our GWAMA in European-origin participants weakly predicted the crude twinning rates in 47 non-European populations (r = 0.23 between risk score and population prevalence, s.e. 0.11, 1-tail P = 0.058) indicating that genome-wide association studies (GWAS) are needed in African and Asian populations to explore the causes of their respectively high and low DZ twinning rates. In vivo functional tests in zebrafish for IPO8 validated its essential role in female, but not male, fertility. In most regions, risk SNPs linked to known expression quantitative trait loci (eQTLs). Top SNPs were associated with in vivo reproductive hormone levels with the top pathways including hormone ligand binding receptors and the ovulation cycle.
LARGE SCALE DATA
The full DZT GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/).
LIMITATIONS, REASONS FOR CAUTION
Our study only included European ancestry cohorts. Inclusion of data from Africa (with the highest twining rate) and Asia (with the lowest rate) would illuminate further the biology of twinning and female fertility.
WIDER IMPLICATIONS OF THE FINDINGS
About one in 40 babies born in the world is a twin and there is much speculation on why twinning runs in families. We hope our results will inform investigations of ovarian response in new and existing ARTs and the causes of female infertility.
STUDY FUNDING/COMPETING INTEREST(S)
Support for the Netherlands Twin Register came from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.NL, 184.021.007), Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB, European Research Council (ERC-230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1) and the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951. The QIMR Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). L.Y. is funded by Australian Research Council (Grant number DE200100425). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886) and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). The Women’s Genome Health Study (WGHS) was funded by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with support for genotyping provided by Amgen. Data collection in the Finnish Twin Registry has been supported by the Wellcome Trust Sanger Institute, the Broad Institute, ENGAGE—European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, AA-09203, AA15416, and K02AA018755) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073 and 336823 to J. Kaprio). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. For NESDA, funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10000-1002), the Center for Medical Systems Biology (CSMB, NVVO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University’s Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants 1 RC2 Ml-1089951 and IRC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. Work in the Del Bene lab was supported by the Programme Investissements d’Avenir IHU FOReSIGHT (ANR-18-IAHU-01). C.R. was supported by an EU Horizon 2020 Marie Skłodowska-Curie Action fellowship (H2020-MSCA-IF-2014 #661527). H.S. and K.S. are employees of deCODE Genetics/Amgen. The other authors declare no competing financial interests.
TRIAL REGISTRATION NUMBER
N/A.
Humankind has lived with the danger of endemic, epidemic and pandemic disease for thousands of years. The effects of these outbreaks have often devastated human populations. Sixteen pandemic events ...causing an estimated 147 million deaths have occurred since the eighth century, The Black Death and the influenza pandemic of 1918-1920 probably having the greatest impact.
Animal populations, both wild and domestic, have similarly suffered devastating outbreaks of disease which, on occasions, have translated into serious effects on human health. The deliberate or accidental introduction of animals into virgin areas has given rise to unforeseen disease events occasionally leading to extinction. Similarly, human intent or negligence and the vagaries of nature itself has resulted in ill health and loss of life. This paper describes the history of pandemics, epidemics and disasters, and the attempts to bring them under control.
Changes in the luminescence, infra-red and visible spectra of poly(ethylene terephthalate) (PET) when degraded at melt temperatures in air and nitrogen have been examined. Main chain-scission and ...subsequent aggregation of terephthalate fragments is illustrated by an increase in dimer fluorescence, while the presence of a longer wavelength fluorescence is attributed to aromatic hydroxylation. A longer residence time in the melt leads to a reduction in the intensity of hydroxylated bands consistent with their further oxidation. Phosphorescence studies on oxidised PET and its extracts indicate stilbenequinone-type impurities. Infra-red spectra are consistent with the development of hydroxylated terephthlate units, vinyl esters dicarboxylic acids and quinones. Lack of symmetry in the charge-transfer bands of the visible spectra of degraded PET reinforce the findings from luminescence and infra-red spectra, indicating that for short residence times in the melt polyconjugated species are not responsible for yellowing.
The effect of locally applied prazosin on pupillometric measures was studied in healthy volunteers, in an attempt to identify the role of α1‐adrenoceptors in the recovery time of the light reflex. ...Prazosin antagonized the mydriatic effect of phenylephrine, but did not alter that of tropicamide. Miotic responses to a range of light stimuli were measured under ambient temperature conditions of 22° C and 40° C. The 40° C condition was associated with shorter recovery times of the light reflex; prazosin increased the recovery time under both temperature conditions. Response amplitude was not affected by the temperature condition or prazosin. The results are consistent with the hypothesis that sympathetic neuromuscular transmission is involved in the redilatation of the pupil following a miotic response to light stimulation.
The etiology and pathogenesis of endometriosis are complex with both genetic and environmental factors contributing to disease risk. Genome-wide association studies (GWAS) have identified multiple ...signals in the estrogen receptor 1 (ESR1) region associated with endometriosis and other reproductive traits and diseases. In addition, candidate gene association studies identified signals in the ESR1 region associated with endometriosis risk suggesting genetic regulation of genes in this region may be important for reproductive health. This study aimed to investigate hormonal and genetic regulation of genes in the ESR1 region in human endometrium. Changes in serum oestradiol and progesterone concentrations and expression of hormone receptors ESR1 and progesterone receptor (PGR) were assessed in endometrial samples from 135 women collected at various stages of the menstrual cycle. Correlation between hormone concentrations, receptor expression and expression of genes in the ESR1 locus was investigated. The effect of endometriosis risk variants on expression of genes in the region was analyzed to identify gene targets. Hormone concentrations and receptor expression varied significantly across the menstrual cycle. Expression of genes in the ESR1 region correlated with progesterone concentration; however, they were more strongly correlated with expression of ESR1 and PGR suggesting coregulation of genes. There was no evidence that endometriosis risk variants directly regulated expression of genes in the region. Limited sample size and cellular heterogeneity in endometrial tissue may impact the ability to detect significant genetic effects on gene expression. Effects of these variants should be validated in a larger dataset and in relevant individual cell types.
The etiology and pathogenesis of endometriosis are complex with both genetic and environmental factors contributing to disease risk. Genome-wide association studies (GWAS) have identified multiple ...signals in the estrogen receptor 1 (ESR1) region associated with endometriosis and other reproductive traits and diseases. In addition, candidate gene association studies identified signals in the ESR1 region associated with endometriosis risk suggesting genetic regulation of genes in this region may be important for reproductive health. This study aimed to investigate hormonal and genetic regulation of genes in the ESR1 region in human endometrium. Changes in serum oestradiol and progesterone concentrations and expression of hormone receptors ESR1 and progesterone receptor (PGR) were assessed in endometrial samples from 135 women collected at various stages of the menstrual cycle. Correlation between hormone concentrations, receptor expression and expression of genes in the ESR1 locus was investigated. The effect of endometriosis risk variants on expression of genes in the region was analyzed to identify gene targets. Hormone concentrations and receptor expression varied significantly across the menstrual cycle. Expression of genes in the ESR1 region correlated with progesterone concentration; however, they were more strongly correlated with expression of ESR1 and PGR suggesting coregulation of genes. There was no evidence that endometriosis risk variants directly regulated expression of genes in the region. Limited sample size and cellular heterogeneity in endometrial tissue may impact the ability to detect significant genetic effects on gene expression. Effects of these variants should be validated in a larger dataset and in relevant individual cell types.
Enzyme-multiplied immunoassay techniques (EMIT) are now widely used as an effective method for monitoring gentamicin concentrations to ensure adequate serum levels. The current EMIT system was to be ...superseded by an improved version and both were run in parallel over a nine-month period and the results compared. During this time the systems were evaluated for ease of use, and reproducibility of results. The newer, EMIT produced more consistent calibration results with less kit-to-kit variation, which in turn gave more reproducible results both with patients' sera and the monthly NEQAS quality controls. The newer system was put into routine use at the end of the trial.
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