22 research outputs found

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

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    Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

    Keep It Movin': Discovering motile ciliated cell types in the central nervous system

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    Non-communicable diseases are the leading cause of early death and disability worldwide. Among these diseases, idiopathic scoliosis affects approximately 4% of the world’s seemingly healthy children. Additionally, the burden of patient care is significant; hospital stays for a child affected with scoliosis costs five times more than the average hospital stay. Despite these considerations, we have seen a decrease in school screening for the disease and a lack of biological and epidemiological research regarding the condition. Consequently, we know very little about the etiology of the disease, let alone a possible cure. Animal models can help advance our understanding of disease, and the Burdine lab previously used zebrafish to demonstrate an association between cilia motility and spinal curvature in a model of idiopathic scoliosis. I took advantage of the external development, transparency and genetic tractability of zebrafish to probe the heterogeneity of cells expressing motile cilia at juvenile stages. Single cell RNA sequencing of cells with motile cilia, followed by clustering analysis, revealed a large population of radial glial and neural progenitor cells. Notably, there was an absence of cells expressing ependymal markers. This suggests that either a technical issue prevented our identification of this cell type, or that ependymal cells are not the prime motile ciliated cells lining the brain ventricles and spinal canal at this stage. The second goal of my project was to generate zebrafish mutant for the idiopathic scoliosis candidate gene POC5, which has common single nucleotide variations among affected individuals, using vii CRISPR/Cas9 strategies. We were able to generate a POC5 mutant zebrafish with a truncation in the protein that led to scoliotic-like curvature. My studies therefore advance our understanding regarding the motile ciliated cellular composition of the central nervous system. Furthermore, we generate more zebrafish with defective cilia to further elucidate the role of cilia in maintain spine linearity. Overall, I have laid the ground work for continuing studies on the etiology of idiopathic scoliosis, which is necessary for the ultimate transfer of research achievements to therapeutic treatment development and clinical practices

    Moving and thinking behind bars: the effectiveness of an exercise and health education program on psychological distress of incarcerated people with, or at risk of developing, a chronic illness

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    Rates of chronic illness within the New South Wales, Australia, prison population are alarmingly high. Population approaches to health care and community development pose some unique challenges in the context of prisons. These challenges are discussed in the context of the report on the results of a small pilot randomised control trial conducted within one New South Wales prison that investigated the effect of a 12-week exercise and health education program on male inmates\u27 psychological distress. The exercise program targeted individuals with a chronic illness, those who had two or more risk factors for developing a chronic illness and/or inmates over 40 years of age. The psychological distress of the inmate participants was measured weekly using a modified Kessler 10 tool. No statistically significant differences were found between the groups pre- or post- the exercise program. There was also no significant correlation between total psychological distress and participating or not participating in the exercise. A further study, with a larger sample size and different tool, is recommended

    Fit for prison: special population health and fitness programme evaluation

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    Objective. To evaluate a health and fitness programme conducted within a New South Wales, Australia correctional facility for male inmates with a chronic illness. Design. A randomised control trial. Sample. Twenty male inmate participants with a chronic illness, two risk factors for developing a chronic illness or who were over the age of 40 years. Measurements. Pre and post programme health assessments that included resting blood pressure and heart rate, weight, body mass index, waist girth, peak flow measures, peripheral saturation of oxygen, blood glucose levels and 6 minute walk test. Intervention. A 12-week structured exercise programme focusing on cardio respiratory endurance, strength and flexibility training. Results. Statistically significant improvements in resting heart rate and endurance were found. Conclusions. The health and fitness programme positively impacts on the health of inmates with a chronic illness. A further study with a larger sample size would be productive

    COMPARISON OF PRESSURIZED LIQUID EXTRACTION AND MATRIX SOLID-PHASE DISPERSION FOR THE MEASUREMENT OF SEMIVOLATILE ORGANIC COMPOUND ACCUMULATION IN TADPOLES

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    Abstract—Analytical methods capable of trace measurement of semivolatile organic compounds (SOCs) are necessary to assess the exposure of tadpoles to contaminants as a result of long-range and regional atmospheric transport and deposition. The present study compares the results of two analytical methods, one using pressurized liquid extraction (PLE) and the other using matrix solid-phase dispersion (MSPD), for the trace measurement of more than 70 SOCs in tadpole tissue, including current-use pesticides. The MSPD method resulted in improved SOC recoveries and precision compared to the PLE method. The MSPD method also required less time, consumed less solvent, and resulted in the measurement of a greater number of SOCs than the PLE method. Keywords—Tadpoles Semivolatile organic compounds Pesticides Pressurized liquid extraction Matrix solid-phase dispersio
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