545 research outputs found

    An X-ray absorption spectroscopic study at the mercury LIII edge on phenylmercury(II) oxygen species

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    The X-ray absorption spectra of the reference and model compounds HgCl2, PhHgCl, PhHgOAc and [(PhHg)2OH][BF4].H2O have been analysed in both the XANES and EXAFS regions, and the technique was extended to determine the structures of (PhHg)2O, PhHgOH, and the basic salts PhHgOH.PhHgNO3 and PhHgOH.(PhHg)2SO4, which were previously structurally uncharacterised. Results indicate that (PhHg)2O is a molecular species with Hg-O-Hg 135°, while PhHgOH contains the [(PhHg)2OH]+ cation and is better formulated as [(PhHg)2OH]OH. The same cation is also featured in the two basic salts. Electrospray mass spectral studies of PhHgOH in aqueous solutions show that [PhHgOH2]+, [(PhHg)2OH]+ and [(PhHg)3O]+ co-exist in solution in a pH-dependent equilibrium

    The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

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    &lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

    Maternal super-obesity and perinatal outcomes in Australia: A national population-based cohort study

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    © 2015 Sullivan et al. Background: Super-obesity is associated with significantly elevated rates of obstetric complications, adverse perinatal outcomes and interventions. The purpose of this study was to determine the prevalence, risk factors, management and perinatal outcomes of super-obese women giving birth in Australia. Methods: A national population-based cohort study. Super-obese pregnant women (body mass index (BMI) >50 kg/m2 or weight >140 kg) who gave birth between January 1 and October 31, 2010 and a comparison cohort were identified using the Australasian Maternity Outcomes Surveillance System (AMOSS). Outcomes included maternal and perinatal morbidity and mortality. Prevalence estimates calculated with 95 % confidence intervals (CIs). Adjusted odds ratios (ORs) were calculated using multivariable logistic regression. Results: 370 super-obese women with a median BMI of 52.8 kg/m2 (range 40.9-79.9 kg/m2) and prevalence of 2.1 per 1 000 women giving birth (95 % CI: 1.96-2.40). Super-obese women were significantly more likely to be public patients (96.2 %), smoke (23.8 %) and be socio-economically disadvantaged (36.2 %). Compared with other women, super-obese women had a significantly higher risk for obstetric (adjusted odds ratio (AOR) 2.42, 95 % CI: 1.77-3.29) and medical (AOR: 2.89, 95 % CI: 2.64-4.11) complications during pregnancy, birth by caesarean section (51.6 %) and admission to special care (HDU/ICU) (6.2 %). The 372 babies born to 365 super-obese women with outcomes known had significantly higher rates of birthweight ≥4500 g (AOR 19.94, 95 % CI: 6.81-58.36), hospital transfer (AOR 3.81, 95 % CI: 1.93-7.55) and admission to Neonatal Intensive Care Unit (NICU) (AOR 1.83, 95 % CI: 1.27-2.65) compared to babies of the comparison group, but not prematurity (10.5 % versus 9.2 %) or perinatal mortality (11.0 (95 % CI: 4.3-28.0) versus 6.6 (95 % CI: 2.6- 16.8) per 1 000 singleton births). Conclusions: Super-obesity in pregnancy in Australia is associated with increased rates of pregnancy and birth complications, and with social disadvantage. There is an urgent need to further address risk factors leading to super-obesity among pregnant women and for maternity services to better address pre-pregnancy and pregnancy care to reduce associated inequalities in perinatal outcomes

    The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

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    PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    Fine Mapping of the Bsr1 Barley Stripe Mosaic Virus Resistance Gene in the Model Grass Brachypodium distachyon

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    The ND18 strain of Barley stripe mosaic virus (BSMV) infects several lines of Brachypodium distachyon, a recently developed model system for genomics research in cereals. Among the inbred lines tested, Bd3-1 is highly resistant at 20 to 25°C, whereas Bd21 is susceptible and infection results in an intense mosaic phenotype accompanied by high levels of replicating virus. We generated an F6∶7 recombinant inbred line (RIL) population from a cross between Bd3-1 and Bd21 and used the RILs, and an F2 population of a second Bd21 × Bd3-1 cross to evaluate the inheritance of resistance. The results indicate that resistance segregates as expected for a single dominant gene, which we have designated Barley stripe mosaic virus resistance 1 (Bsr1). We constructed a genetic linkage map of the RIL population using SNP markers to map this gene to within 705 Kb of the distal end of the top of chromosome 3. Additional CAPS and Indel markers were used to fine map Bsr1 to a 23 Kb interval containing five putative genes. Our study demonstrates the power of using RILs to rapidly map the genetic determinants of BSMV resistance in Brachypodium. Moreover, the RILs and their associated genetic map, when combined with the complete genomic sequence of Brachypodium, provide new resources for genetic analyses of many other traits

    Obesity dysregulates the pulmonary antiviral immune response

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    Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals

    FGF Signaling Inhibition in ESCs Drives Rapid Genome-wide Demethylation to the Epigenetic Ground State of Pluripotency

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    SummaryGenome-wide erasure of DNA methylation takes place in primordial germ cells (PGCs) and early embryos and is linked with pluripotency. Inhibition of Erk1/2 and Gsk3β signaling in mouse embryonic stem cells (ESCs) by small-molecule inhibitors (called 2i) has recently been shown to induce hypomethylation. We show by whole-genome bisulphite sequencing that 2i induces rapid and genome-wide demethylation on a scale and pattern similar to that in migratory PGCs and early embryos. Major satellites, intracisternal A particles (IAPs), and imprinted genes remain relatively resistant to erasure. Demethylation involves oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), impaired maintenance of 5mC and 5hmC, and repression of the de novo methyltransferases (Dnmt3a and Dnmt3b) and Dnmt3L. We identify a Prdm14- and Nanog-binding cis-acting regulatory region in Dnmt3b that is highly responsive to signaling. These insights provide a framework for understanding how signaling pathways regulate reprogramming to an epigenetic ground state of pluripotency

    Taking Ownership: Our Pledge to Educate All of Detroit's Children

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    Excellent Schools Detroit represents a broad and diverse cross section of Detroit's education, government, civic and community, parent, organized labor, and philanthropic leaders who are committed to ensuring that all Detroit children receive the great education they deserve. This citywide education plan reflects months of discussions and deliberations by coalition members, as well as a series of six community meetings in November and December, youth focus groups, small group discussions with multiple stakeholders, and other outreach efforts. We appreciate the thoughtful recommendations from the many Detroiters who are as passionate as we are about the need to prepare all students for college, careers, and life in the 21st century
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