441 research outputs found

    Aerobic co-composting degradation of highly PCDD/F-contaminated field soil. A study of bacterial community

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    Β© 2018 Elsevier B.V. This study investigated bacterial communities during aerobic food waste co-composting degradation of highly PCDD/F-contaminated field soil. The total initial toxic equivalent quantity (TEQ) of the soil was 16,004 ng-TEQ kg βˆ’1 dry weight. After 42-day composting and bioactivity-enhanced monitored natural attenuation (MNA), the final compost product's TEQ reduced to 1916 ng-TEQ kg βˆ’1 dry weight (approximately 75% degradation) with a degradation rate of 136.33 ng-TEQ kg βˆ’1 day βˆ’1 . Variations in bacterial communities and PCDD/F degraders were identified by next-generation sequencing (NGS). Thermophilic conditions of the co-composting process resulted in fewer observed bacteria and PCDD/F concentrations. Numerous organic compound degraders were identified by NGS, supporting the conclusion that PCDD/Fs were degraded during food waste co-composting. Bacterial communities of the composting process were defined by four phyla (Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes). At the genus level, Bacillus (Firmicutes) emerged as the most dominant phylotype. Further studies on specific roles of these bacterial strains are needed, especially for the thermophiles which contributed to the high degradation rate of the co-co-composting treatment's first 14 days

    MAXIPOL: a balloon-borne experiment for measuring the polarization anisotropy of the cosmic microwave background radiation

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    We discuss MAXIPOL, a bolometric balloon-borne experiment designed to measure the E-mode polarization anisotropy of the cosmic microwave background radiation (CMB) on angular scales of 10 arcmin to 2 degrees. MAXIPOL is the first CMB experiment to collect data with a polarimeter that utilizes a rotating half-wave plate and fixed wire-grid polarizer. We present the instrument design, elaborate on the polarimeter strategy and show the instrument performance during flight with some time domain data. Our primary data set was collected during a 26 hour turnaround flight that was launched from the National Scientific Ballooning Facility in Ft. Sumner, New Mexico in May 2003. During this flight five regions of the sky were mapped. Data analysis is in progress

    An instability criterion for nonlinear standing waves on nonzero backgrounds

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    A nonlinear Schr\"odinger equation with repulsive (defocusing) nonlinearity is considered. As an example, a system with a spatially varying coefficient of the nonlinear term is studied. The nonlinearity is chosen to be repelling except on a finite interval. Localized standing wave solutions on a non-zero background, e.g., dark solitons trapped by the inhomogeneity, are identified and studied. A novel instability criterion for such states is established through a topological argument. This allows instability to be determined quickly in many cases by considering simple geometric properties of the standing waves as viewed in the composite phase plane. Numerical calculations accompany the analytical results.Comment: 20 pages, 11 figure

    Mismatch Repair–Independent Increase in Spontaneous Mutagenesis in Yeast Lacking Non-Essential Subunits of DNA Polymerase Ξ΅

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    Yeast DNA polymerase Ξ΅ (Pol Ξ΅) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template. In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol Ξ΅ also has one essential subunit (Dpb2) and two smaller, non-essential subunits (Dpb3 and Dpb4) whose functions are not fully understood. To probe the functions of Dpb3 and Dpb4, here we investigate the consequences of their absence on the biochemical properties of Pol Ξ΅ in vitro and on genome stability in vivo. The fidelity of DNA synthesis in vitro by purified Pol2/Dpb2, i.e. lacking Dpb3 and Dpb4, is comparable to the four-subunit Pol Ξ΅ holoenzyme. Nonetheless, deletion of DPB3 and DPB4 elevates spontaneous frameshift and base substitution rates in vivo, to the same extent as the loss of Pol Ξ΅ proofreading activity in a pol2-4 strain. In contrast to pol2-4, however, the dpb3Ξ”dpb4Ξ” does not lead to a synergistic increase of mutation rates with defects in DNA mismatch repair. The increased mutation rate in dpb3Ξ”dpb4Ξ” strains is partly dependent on REV3, as well as the proofreading capacity of Pol Ξ΄. Finally, biochemical studies demonstrate that the absence of Dpb3 and Dpb4 destabilizes the interaction between Pol Ξ΅ and the template DNA during processive DNA synthesis and during processive 3β€² to 5β€²exonucleolytic degradation of DNA. Collectively, these data suggest a model wherein Dpb3 and Dpb4 do not directly influence replication fidelity per se, but rather contribute to normal replication fork progression. In their absence, a defective replisome may more frequently leave gaps on the leading strand that are eventually filled by Pol ΞΆ or Pol Ξ΄, in a post-replication process that generates errors not corrected by the DNA mismatch repair system

    Chemical treatment enhances skipping of a mutated exon in the dystrophin gene

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    Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by a loss of the dystrophin protein. Control of dystrophin mRNA splicing to convert severe DMD to a milder phenotype is attracting much attention. Here we report a dystrophinopathy patient who has a point mutation in exon 31 of the dystrophin gene. Although the mutation generates a stop codon, a small amount of internally deleted, but functional, dystrophin protein is produced in the patient cells. An analysis of the mRNA reveals that the mutation promotes exon skipping and restores the open reading frame of dystrophin. Presumably, the mutation disrupts an exonic splicing enhancer and creates an exonic splicing silencer. Therefore, we searched for small chemicals that enhance exon skipping, and found that TG003 promotes the skipping of exon 31 in the endogenous dystrophin gene in a dose-dependent manner and increases the production of the dystrophin protein in the patient's cells

    Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

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    DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1β€”together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteinsβ€”define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

    Interaction of hnRNPA1/A2 and DAZAP1 with an Alu-Derived Intronic Splicing Enhancer Regulates ATM Aberrant Splicing

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    We have previously identified an Alu-derived Intronic Splicing enhancer (ISE) in the Ataxia Teleangectasia Mutated gene (ATM) that facilitates intron pre-mRNA processing and leads to the inclusion of a cryptic exon in the final mRNA transcript. By using an RNA pull-down assay, we show here that hnRNPA1/A2, HuR and DAZAP1 splicing factors and DHX36 RNA helicase bind to the ISE. By functional studies (overexpression and siRNA experiments), we demonstrate that hnRNPA1 and DAZAP1 are indeed involved in ISE-dependent ATM cryptic exon activation, with hnRNPA1 acting negatively and DAZAP1 positively on splicing selection. On the contrary, HuR and DHX36 have no effect on ATM splicing pattern. These data suggest that splicing factors with both negative and positive effect can assemble on the intronic Alu repeats and regulate pre-mRNA splicing

    A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women

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    Background Anemia due to iron deficiency is recognized as one of the major nutritional deficiencies in women and children in developing countries. Daily iron supplementation for pregnant women is recommended in many countries although there are few reports of these programs working efficiently or effectively. Weekly iron-folic acid supplementation (WIFS) and regular deworming treatment is recommended for non-pregnant women living in areas with high rates of anemia. Following a baseline survey to assess the prevalence of anemia, iron deficiency and soil transmitted helminth infections, we implemented a program to make WIFS and regular deworming treatment freely and universally available for all women of reproductive age in two districts of a province in northern Vietnam over a 12 month period. The impact of the program at the population level was assessed in terms of: i) change in mean hemoglobin and iron status indicators, and ii) change in the prevalence of anemia, iron deficiency and hookworm infections. Method Distribution of WIFS and deworming were integrated with routine health services and made available to 52,000 women. Demographic data and blood and stool samples were collected in baseline, and three and 12-month post-implementation surveys using a population-based, stratified multi-stage cluster sampling design. Results The mean Hb increased by 9.6 g/L (95% CI, 5.7, 13.5, p < 0.001) during the study period. Anemia (Hb<120 g/L) was present in 131/349 (37.5%, 95% CI 31.3, 44.8) subjects at baseline, and in 70/363 (19.3%, 95% CI 14.0, 24.6) after twelve months. Iron deficiency reduced from 75/329 (22.8%, 95% CI 16.9, 28.6) to 33/353 (9.3%, 95% CI 5.7, 13.0) by the 12-mnth survey, and hookworm infection from 279/366 (76.2%,, 95% CI 68.6, 83.8) to 66/287 (23.0%, 95% CI 17.5, 28.5) over the same period. Conclusion A free, universal WIFS program with regular deworming was associated with reduced prevalence and severity of anemia, iron deficiency and h

    Artesunate induces necrotic cell death in schwannoma cells

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    Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity
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