108 research outputs found
The kinetics of the reaction of superoxide radical with Fe(III) complexes of EDTA, DETAPAC and HEDTA
AbstractTo gain an understanding of the mechanism by which the hydroxyl free radical can arise in superoxide generating systems and learn how different chelaters of iron can inhibit this reaction, a pulse radiolysis kinetic study of the reaction of Oâ2 with Fe(III)EDTA, Fe(III)HEDTA and Fe(III)DETAPAC (or DTPA) was undertaken. Superoxide reacts readily with Fe(III)EDTA and Fe(III)HEDTA with a pH-dependent second-order rate constant having values of 1.9 Ă 106 Mâ1.sâ1 and 7.6 Ă 105 Mâ1.sâ1 at pH 7, respectively. However, the rate constant for the reaction of Oâ2 with Fe(III)DETAPAC was found to be much slower, the upper limit for the rate constant being 104 Mâ1.sâ1. These results in conjunction with spin-trapping experiments with Fe(II)EDTA, Fe(II)HEDTA, Fe(II)DETAPAC and H2O2 suggests that DETAPAC inhibits the formation of OH by slowing the reduction of Fe(III) to Fe(II) and not by inhibiting the Fenton reaction
Structureâactivity relationships in hydroxy-2,3-diarylxanthone antioxidants. Fast kinetics spectroscopy as a tool to evaluate the potential for antioxidant activity in biological systems
A structureâactivity relationship has been established for eight hydroxy-2,3-diarylxanthones (XH)
bearing hydroxy groups on the two aryl rings. One-electron oxidation by superoxide radical-anions
(ÎŁO2
-) and ÎŁTrp radicals as well as reaction with ÎŁCCl3O2 and ÎŁCHCl2O2 radicals demonstrates that two
OH groups are required for efficient antioxidant reactivity in cetyltrimethylammonium bromide
micelles. Hydroxy groups at the meta and para positions on either of the two phenyl rings confer
enhanced reactivity, but XH bearing an OH at the para position of either phenyl ring is unreactive.
While oxidation is favoured by OH in both meta and para positions of 2-aryl xanthone substituents,
addition of a third and/or fourth OH enhances electron-donating capacity. In Cu2+-induced lipid
peroxidation of human LDL, the lag period preceding the commencement of lipid peroxidation in the
presence of XH bearing OH at meta and para positions on the 3-phenyl ring is extended to twice that
observed with a comparable concentration of quercetin, a reference antioxidant. These antioxidants are
also superior to quercetin in protecting human skin keratinocytes against tert-butylhydroperoxideinduced
oxidative stress. While XH antioxidant activity in model biological systems is consistent with
the structureâactivity relationship, their response is also modulated by the localization of XH and by
structural factors.This is Document No. NDLR-4864 from the Notre Dame
Radiation Laboratory which is supported by the Office of Basic
Energy Sciences at the United States Department of Energy.
This work was supported by the Franco-Portuguese exchange
programs GRICES-INSERM 2005-2006 and Pessoa 07958NF.
P. Filipe thanks the âSociedade Portugesa de Dermatologia e
Venerologiaâ for a travel grant. Thanks are due to the University
of Aveiro, âFundação para a CiĂȘncia e a Tecnologiaâ and FEDER for funding the Organic Chemistry Research Unit.
Clementina M. M. Santos thanks the Calouste Gulbenkian
Foundation for the award of a short period research grant
(proc 87872)
The dependence of alpha-tocopheroxyl radical reduction by hydroxy-2,3-diarylxanthones on structure and micro-environment
The flavonoid quercetin is known to reduce the α-tocopheroxyl radical (ËTocO) and reconstitute
α-tocopherol (TocOH). Structurally related polyphenolic compounds, hydroxy-2,3-diarylxanthones (XH),
exhibit antioxidant activity which exceeds that of quercetin in biological systems. In the present study
repair of ËTocO by a series of these XH has been evaluated using pulse radiolysis. It has been shown that,
among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H-xanthen-9-one (XH9) reduces ËTocO,
though repair depends strongly on the micro-environment. In cationic cetyltrimethylammonium bromide
(CTAB) micelles, 30% of ËTocO radicals are repaired at a rate constant of âŒ7.4 Ă 106 Mâ1 sâ1 by XH9
compared to 1.7 Ă 107 Mâ1 sâ1 by ascorbate. Water-soluble Trolox (TrOH) radicals (ËTrO) are restored by
XH9 in CTAB (rate constant âŒ3 Ă 104 Mâ1 sâ1) but not in neutral TX100 micelles where only 15% of
ËTocO are repaired (rate constant âŒ4.5 Ă 105 Mâ1 sâ1). In basic aqueous solutions ËTrO is readily reduced
by deprotonated XH9 species leading to ionized XH9 radical species (radical pKa âŒ10). An equilibrium is
observed (K = 130) yielding an estimate of 130 mV for the reduction potential of the [ËX9,H+/XH9]
couple at pH 11, lower than the 250 mV for the [ËTrO,H+/TrOH] couple. A comparable value (100 mV)
has been determined by cyclic voltammetry measurements
Body Burdens of Polybrominated Diphenyl Ethers among Urban Anglers
Polybrominated diphenyl ethers (PBDEs) have been widely used in the United States and worldwide as flame retardants. Recent PBDE production figures show that worldwide use has increased. To determine whether fish consumption is a source of PBDE exposure for humans, a cross-sectional epidemiologic study of New York and New Jersey urban anglers was conducted during the summers of 2001â2003. Frequency of local fish consumption was assessed by questionnaire, and blood samples for PBDE analysis were collected from 94 anglers fishing from piers on the lower Hudson River and Newark Bay. We analyzed PBDEs by gas chromatographyâisotope dilutionâhigh-resolution mass spectrometry. The congeners found in anglersâ serum at the highest concentrations were, by International Union of Pure and Applied Chemistry numbers, BDE-47, BDE-153, and BDE-99. Anglers reporting consumption of local fish had higher, but nonstatistically significantly different, concentrations of PBDEs than did anglers who did not eat local fish. For some congeners (BDE-100 and BDE-153), we observed moderate doseâresponse relationships between serum PBDE levels and frequency of reported fish intake. These findings suggest that consumption of locally caught fish is not a major route of human exposure for this study population
Differences in adjustment by child developmental stage among caregivers of children with disorders of sex development
<p>Abstract</p> <p>Background</p> <p>The current study sought to compare levels of overprotection and parenting stress reported by caregivers of children with disorders of sex development at four different developmental stages.</p> <p>Methods</p> <p>Caregivers (<it>N </it>= 59) of children with disorders of sex development were recruited from specialty clinics and were asked to complete the Parent Protection Scale and Parenting Stress Index/Short Form as measures of overprotective behaviors and parenting stress, respectively.</p> <p>Results</p> <p>Analyses of covariance (ANCOVAs) were conducted to examine differences between caregiver report of overprotection and parenting stress. Results revealed that caregivers of infants and toddlers exhibited more overprotective behaviors than caregivers of children in the other age groups. Further, caregivers of adolescents experienced significantly more parenting stress than caregivers of school-age children, and this effect was driven by personal distress and problematic parent-child interactions, rather than having a difficult child.</p> <p>Conclusions</p> <p>These results suggest that caregivers of children with disorders of sex development may have different psychosocial needs based upon their child's developmental stage and based upon the disorder-related challenges that are most salient at that developmental stage.</p
Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children
Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry
Variations on a theme: diversification of cuticular hydrocarbons in a clade of cactophilic Drosophila
<p>Abstract</p> <p>Background</p> <p>We characterized variation and chemical composition of epicuticular hydrocarbons (CHCs) in the seven species of the <it>Drosophila buzzatii </it>cluster with gas chromatography/mass spectrometry. Despite the critical role of CHCs in providing resistance to desiccation and involvement in communication, such as courtship behavior, mating, and aggregation, few studies have investigated how CHC profiles evolve within and between species in a phylogenetic context. We analyzed quantitative differences in CHC profiles in populations of the <it>D. buzzatii </it>species cluster in order to assess the concordance of CHC differentiation with species divergence.</p> <p>Results</p> <p>Thirty-six CHC components were scored in single fly extracts with carbon chain lengths ranging from C<sub>29 </sub>to C<sub>39</sub>, including methyl-branched alkanes, <it>n</it>-alkenes, and alkadienes. Multivariate analysis of variance revealed that CHC amounts were significantly different among all species and canonical discriminant function (CDF) analysis resolved all species into distinct, non-overlapping groups. Significant intraspecific variation was found in different populations of <it>D. serido </it>suggesting that this taxon is comprised of at least two species. We summarized CHC variation using CDF analysis and mapped the first five CHC canonical variates (CVs) onto an independently derived <it>period </it>(<it>per</it>) gene + chromosome inversion + mtDNA COI gene for each sex. We found that the COI sequences were not phylogenetically informative due to introgression between some species, so only <it>per </it>+ inversion data were used. Positive phylogenetic signal was observed mainly for CV1 when parsimony methods and the test for serial independence (TFSI) were used. These results changed when no outgroup species were included in the analysis and phylogenetic signal was then observed for female CV3 and/or CV4 and male CV4 and CV5. Finally, removal of divergent populations of <it>D. serido </it>significantly increased the amount of phylogenetic signal as up to four out of five CVs then displayed positive phylogenetic signal.</p> <p>Conclusions</p> <p>CHCs were conserved among species while quantitative differences in CHC profiles between populations and species were statistically significant. Most CHCs were species-, population-, and sex-specific. Mapping CHCs onto an independently derived phylogeny revealed that a significant portion of CHC variation was explained by species' systematic affinities indicating phylogenetic conservatism in the evolution of these hydrocarbon arrays, presumptive waterproofing compounds and courtship signals as in many other drosophilid species.</p
Recommended from our members
Homologous recombination DNA repair defects in PALB2- associated breast cancers
Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD
Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences
The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & NemĂ©sio 2007; Donegan 2008, 2009; NemĂ©sio 2009aâb; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported
by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on
18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based
researchers who signed it in the short time span from 20 September to 6 October 2016
- âŠ