24 research outputs found

    Understanding precision nitrogen stress to optimize the growth and lipid content tradeoff in oleaginous green microalgae

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    Nitrogen deficiency promotes lipid formation in many microalgae, but also limits growth and lipid productivity. In spite of numerous studies, there is poor understanding of the interactions of growth and lipid content, the time course of lipid accumulation and the magnitude of nitrogen deficiency required to stimulate lipid formation. These relationships were investigated in six species of oleaginous green algae, comparing high and low levels of deficiency. Nitrogen stress typically had disproportionate effects on growth and lipid content, with profound differences among species. Optimally balancing the tradeoffs required a wide range in nitrogen supply rate among species. Some species grew first and then accumulated lipids, while other species grew and accumulated lipids concurrently which resulted in increased lipid productivity. Accumulation of high lipid content generally resulted from a response to minimal stress. The data highlight the tremendous biodiversity that may be exploited to optimally produce lipids with precision nitrogen stress

    Human Factors Applications of Biomechanical Modeling

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    Biomechanical data collection and modeling has applications to the field of human factors. Specifically, motion data can be used to determine the operational volume necessary for performing a task. The operational volume assessment can be performed in order to determine how much volume is needed to perform the task or if task performance can be contained and adequately performed within an allocated volume. Motion and external force data, along with computational modeling techniques, can be used to estimate the internal loading produced during performance of a task. Internal loading estimates can be used to determine if an adequate stimulus is generated for maintenance of musculoskeletal health and also for comparison to injury thresholds to determine injury risk during task performance

    Metabolic pathways and immunometabolism in rare kidney diseases

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    Objectives To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. Methods Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups. Correlation analyses measured relationships between metabolic pathways, kidney function and cytokine production. Results Reduced steady state levels of mRNA species were enriched in pathways of oxidative phosphorylation and increased in the pentose phosphate pathway (PPP) with maximal perturbation in AAV and SLE followed by NS, and least in LD. Transcript regulation was isozymes specific with robust regulation in hexokinases, enolases and glucose transporters. Intercorrelation networks were observed between enzymes of the PPP (eg, transketolase) and macrophage markers (eg, CD68) (r=0.49, p<0.01). Increased PPP transcript levels were associated with reduced glomerular filtration rate in the glomerular (r=-0.49, p<0.01) and tubulointerstitial (r=-0.41, p<0.01) compartments. PPP expression and tumour necrosis factor activation were tightly co-expressed (r=0.70, p<0.01). Conclusion This study demonstrated concordant alterations of the renal transcriptome consistent with metabolic reprogramming across different forms of glomerulonephritis. Activation of the PPP was tightly linked with intrarenal macrophage marker expression, reduced kidney function and increased production of cytokines. Modulation of glucose metabolism may offer novel immune-modulatory therapeutic approaches in rare kidney diseases

    Visual consumption, collective memory and the representation of war

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    Conceiving of the visual as a significant force in the production and dissemination of collective memory, we argue that a new genre of World War Two films has recently emerged that form part of a new discursive “regime of memory” about the war and those that fought and lived through it, constituting a commemoration as much about reflecting on the present as it is about remembering the past. First, we argue that these films seek to reaffirm a (particular conception of a) US national identity and military patriotism in the post–Cold War era by importing World War Two as the key meta‐narrative of America’s relationship to war in order to “correct” and help “erase” Vietnam’s more negative discursive rendering. Second, we argue that these films attempt to rewrite the history of World War Two by elevating and illuminating the role of the US at the expense of the Allies, further serving to reaffirm America’s position of political and military dominance in the current age, and third, that these films form part of a celebration of the generation that fought World War Two, which may accord them a position of nostalgic and sentimental greatness, as their collective spirit and notions of duty and service shine against the foil of what might frequently be seen as our own present moral ambivalence

    Discipline-informed approaches to water accounting

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    Recent decades have witnessed demands for greater transparency and more clearly defined lines of responsibility and accountability in the management of natural resources. Consequently, various approaches to recording and reporting data relating to such resources have emerged, particularly in relation to water. We explore international water accounting developments where different water accounting systems are being developed in different settings, with different origins, and influenced by different disciplines. Australia is developing a general-purpose water accounting system with its genealogy in financial reporting. We explore its development and implications for regulators and professionals in accounting and water-related business. We also contemplate the potential for a global water accounting system

    PGC1α promoter methylation in blood at 5–7 years predicts adiposity from 9 to 14 years (EarlyBird 50)

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    The early environment, acting via epigenetic processes, is associated with differential risk of cardio-metabolic disease (CMD) which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analysed DNA methylation in the peroxisomal proliferator-?-co-activator-1? promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years by pyrosequencing. Body composition was measured annually by dual x-ray absorptiometry, physical activity by accelerometery and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven CpG loci were identified that showed no significant temporal change or association with leukocyte populations. Modelling using generalised estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing and activity. Methylation of one predictive locus modified binding of the pro-adipogenic PBX-1/HOXB9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk

    DNA methylation of SIRT1, the longevity gene, in blood from children at 5–7 years exhibits temporal stability and predicts adiposity in adolescence

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    <p>Our preliminary findings show that the methylation status of specific CpG loci in the peroxisomal proliferator-gamma-co-activator-(PGC)-1α promoter in blood at age 5-7 years predicted later adiposity in the children age 14 years. PGC1α is a downstream effector of Sirtuin 1 (SIRT1), a gene which has been shown to influence lifespan in a range of species and which is known to regulate energy metabolism in different tissues.</p> <p>We, therefore, have investigated the temporal stability of specific CpG loci within the promoter of SIRT1 during childhood and whether the CpG loci that exhibited temporal stability predicted adiposity.</p

    PI3Kδ Inhibition by Idelalisib in patients with relapsed indolent lymphoma

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    BACKGROUNDPhosphatidylinositol-3-kinase delta (PI3Kδ) mediates B-cell receptor signaling and microenvironmental support signals that promote the growth and survival of malignant B lymphocytes. In a phase 1 study, idelalisib, an orally active selective PI3Kδ inhibitor, showed antitumor activity in patients with previously treated indolent non-Hodgkin's lymphomas.METHODSIn this single-group, open-label, phase 2 study, 125 patients with indolent non-Hodgkin's lymphomas who had not had a response to rituximab and an alkylating agent or had had a relapse within 6 months after receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progressed or the patient withdrew from the study. The primary end point was the overall rate of response; secondary end points included the duration of response, progression-free survival, and safety.RESULTSThe median age of the patients was 64 years (range, 33 to 87); patients had received a median of four prior therapies (range, 2 to 12). Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). The response rate was 57% (71 of 125 patients), with 6% meeting the criteria for a complete response. The median time to a response was 1.9 months, the median duration of response was 12.5 months, and the median progression-free survival was 11 months. Similar response rates were observed across all subtypes of indolent non-Hodgkin's lymphoma, though the numbers were small for some categories. The most common adverse events of grade 3 or higher were neutropenia (in 27% of the patients), elevations in aminotransferase levels (in 13%), diarrhea (in 13%), and pneumonia (in 7%).CONCLUSIONSIn this single-group study, idelalisib showed antitumor activity with an acceptable safety profile in patients with indolent non-Hodgkin's lymphoma who had received extensive prior treatment. (Funded by Gilead Sciences and others; ClinicalTrials.gov number, NCT01282424. opens in new tab.
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