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  • 11
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    Disrupting lipid catabolism increases algal lipids [Applied Biological Sciences] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-12-04
    Description: Biologically derived fuels are viable alternatives to traditional fossil fuels, and microalgae are a particularly promising source, but improvements are required throughout the production process to increase productivity and reduce cost. Metabolic engineering to increase yields of biofuel-relevant lipids in these organisms without compromising growth is an important aspect of...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 12
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    BIRC6 Targeting as Potential Therapy for Advanced, Enzalutamide-Resistant Prostate Cancer (2017)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2017-03-16
    Description: Purpose: Enzalutamide resistance has emerged as a major problem in the management of castration-resistant prostate cancer (CRPC). Research on therapy resistance of CRPCs has primarily focused on the androgen receptor pathway. In contrast, there is limited information on antiapoptotic mechanisms that may facilitate the treatment resistance. The inhibitor of apoptosis proteins (IAP) family is well recognized for its role in promoting treatment resistance of cancers by inhibiting drug-induced apoptosis. Here, we examined whether BIRC6, an IAP family member, has a role in enzalutamide resistance of CRPCs and could provide a therapeutic target for enzalutamide-resistant CRPC. Experimental Design: Use of enzalutamide-resistant CRPC models: (i) the transplantable, first high-fidelity LTL-313BR patient-derived enzalutamide-resistant CRPC tissue xenograft line showing primary enzalutamide resistance, (ii) MR42D and MR49F CRPC cells/xenografts showing acquired enzalutamide resistance. Specific BIRC6 downregulation in these models was produced using a BIRC6 -targeting antisense oligonucleotide (ASO-6w2). Gene expression was determined by qRT-PCR and gene expression profiling. Molecular pathways associated with growth inhibition were assessed via gene enrichment analysis. Results: Of eight IAPs examined, BIRC6 was the only one showing elevated expression in both enzalutamide-resistant CRPC models. Treatment with ASO-6w2 markedly suppressed growth of LTL-313BR xenografts and increased tumor apoptosis without inducing major host toxicity. Pathway enrichment analysis indicated that GPCR and matrisome signaling were the most significantly altered pathways. Furthermore, ASO-6w2 inhibited expression of prosurvival genes that were upregulated in the LTL-313BR line. Conclusions: BIRC6 targeting inhibited the growth of enzalutamide-resistant CRPC models and may represent a new option for clinical treatment of advanced, enzalutamide-resistant prostate cancer. Clin Cancer Res; 23(6); 1542–51. ©2016 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 13
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    The molecular pathogenesis of the NUP98-HOXA9 fusion protein in acute myeloid leukemia (2017)
    Nature Publishing Group (NPG)
    In: Leukemia
    Details
    Publication Date: 2017-09-07
    Description: The molecular pathogenesis of the NUP98-HOXA9 fusion protein in acute myeloid leukemia Leukemia 31, 2000 (September 2017). doi:10.1038/leu.2017.194 Authors: A Rio-Machin, G Gómez-López, J Muñoz, F Garcia-Martinez, A Maiques-Diaz, S Alvarez, R N Salgado, M Shrestha, R Torres-Ruiz, C Haferlach, M J Larráyoz, M J Calasanz, J Fitzgibbon & J C Cigudosa
    Print ISSN: 0887-6924
    Electronic ISSN: 1476-5551
    Topics: Medicine
    Published by Nature Publishing Group (NPG)
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  • 14
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    HIT'nDRIVE: patient-specific multidriver gene prioritization for precision oncology [METHOD] (2017)
    Cold Spring Harbor Laboratory Press
    Details
    Publication Date: 2017-09-02
    Description: Prioritizing molecular alterations that act as drivers of cancer remains a crucial bottleneck in therapeutic development. Here we introduce HIT'nDRIVE, a computational method that integrates genomic and transcriptomic data to identify a set of patient-specific, sequence-altered genes, with sufficient collective influence over dysregulated transcripts. HIT'nDRIVE aims to solve the "random walk facility location" (RWFL) problem in a gene (or protein) interaction network, which differs from the standard facility location problem by its use of an alternative distance measure: "multihitting time," the expected length of the shortest random walk from any one of the set of sequence-altered genes to an expression-altered target gene. When applied to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionable driver genes. We also demonstrated that it is possible to perform accurate phenotype prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interaction networks. In addition, we identified a number of breast cancer subtype-specific driver modules that are associated with patients’ survival outcome. Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer cell lines, accurately predicted drug efficacy using the driver genes and their seeded gene modules. Overall, HIT'nDRIVE may help clinicians contextualize massive multiomics data in therapeutic decision making, enabling widespread implementation of precision oncology.
    Electronic ISSN: 1549-5469
    Topics: Biology , Medicine
    Published by Cold Spring Harbor Laboratory Press
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  • 15
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    Medical students' characteristics as predictors of career practice location: retrospective cohort study tracking graduates of Nepal's first medical college (2012)
    BMJ Publishing Group
    Details
    Publication Date: 2012-08-15
    Description: Objective To determine, in one low income country (Nepal), which characteristics of medical students are associated with graduate doctors staying to practise in the country or in its rural...
    Keywords: Epidemiologic studies, Undergraduate, Medical humanities
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 16
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    Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-05-18
    Description: Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ’s multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys by using unbiased single-cell RNA sequencing. On the basis of gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but share the same phenotypic manifestation originate from the same differentiated cell type. We also found that the collecting duct in kidneys of adult mice generates a spectrum of cell types through a newly identified transitional cell. Computational cell trajectory analysis and in vivo lineage tracing revealed that intercalated cells and principal cells undergo transitions mediated by the Notch signaling pathway. In mouse and human kidney disease, these transitions were shifted toward a principal cell fate and were associated with metabolic acidosis.
    Keywords: Cell Biology, Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 17
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    Ancient lowland Maya complexity as revealed by airborne laser scanning of northern Guatemala (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-09-28
    Description: Lowland Maya civilization flourished in the tropical region of the Yucatan peninsula and environs for more than 2500 years (~1000 BCE to 1500 CE). Known for its sophistication in writing, art, architecture, astronomy, and mathematics, Maya civilization still poses questions about the nature of its cities and surrounding populations because of its location in an inaccessible forest. In 2016, an aerial lidar survey across 2144 square kilometers of northern Guatemala mapped natural terrain and archaeological features over several distinct areas. We present results from these data, revealing interconnected urban settlement and landscapes with extensive infrastructural development. Studied through a joint international effort of interdisciplinary teams sharing protocols, this lidar survey compels a reevaluation of Maya demography, agriculture, and political economy and suggests future avenues of field research.
    Keywords: Anthropology, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 18
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    Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis (2014)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2014-11-08
    Description: Introduction Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients’ remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. Methods and analysis The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. Ethics and dissemination The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration numbers Australia New Zealand Clinical Trials Registry—ACTRN12611000567921; National Institutes of Health—NCT02045121.
    Keywords: Open access, Medical management, Respiratory medicine
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 19
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    Economic costs of chronic disease through lost productive life years (PLYs) among Australians aged 45-64 years from 2015 to 2030: results from a microsimulation model (2016)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2016-09-24
    Description: Objectives To project the number of older workers with lost productive life years (PLYs) due to chronic disease and resultant lost income; and lost taxes and increased welfare payments from 2015 to 2030. Design, setting and participants Using a microsimulation model, Health&WealthMOD2030, the costs of chronic disease in Australians aged 45–64 were projected to 2030. The model integrates household survey data from the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers (SDACs) 2003 and 2009, output from long-standing microsimulation models (STINMOD (Static Incomes Model) and APPSIM (Australian Population and Policy Simulation Model)) used by various government departments, population and labour force growth data from Treasury, and disease trends data from the Australian Burden of Disease and Injury Study (2003). Respondents aged 45–64 years in the SDACs 2003 and 2009 formed the base population. Main outcome measures Lost PLYs due to chronic disease; resultant lost income, lost taxes and increased welfare payments in 2015, 2020, 2025 and 2030. Results We projected 380 000 (6.4%) people aged 45–64 years with lost PLYs in 2015, increasing to 462 000 (6.5%) in 2030—a 22% increase in absolute numbers. Those with lost PLYs experience the largest reduction in income than any other group in each year compared to those employed full time without a chronic disease, and this income gap widens over time. The total economic loss due to lost PLYs consisted of lost income modelled at $A12.6 billion in 2015, increasing to $A20.5 billion in 2030—a 62.7% increase. Additional costs to the government consisted of increased welfare payments at $A6.2 billion in 2015, increasing to $A7.3 billion in 2030—a 17.7% increase; and a loss of $A3.1 billion in taxes in 2015, increasing to $A4.7 billion in 2030—a growth of 51.6%. Conclusions There is a need for greater investment in effective preventive health interventions which improve workers’ health and work capacity.
    Keywords: Open access, Health economics, Public health
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 20
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    Genome-Wide Association Study and QTL Mapping Reveal Genomic Loci Associated with Fusarium Ear Rot Resistance in Tropical Maize Germplasm (2016)
    Genetics Society of America (GSA)
    Details
    Publication Date: 2016-12-08
    Description: Fusarium ear rot (FER) incited by Fusarium verticillioides is a major disease of maize that reduces grain quality globally. Host resistance is the most suitable strategy for managing the disease. We report the results of genome-wide association study (GWAS) to detect alleles associated with increased resistance to FER in a set of 818 tropical maize inbred lines evaluated in three environments. Association tests performed using 43,424 single-nucleotide polymorphic (SNPs) markers identified 45 SNPs and 15 haplotypes that were significantly associated with FER resistance. Each associated SNP locus had relatively small additive effects on disease resistance and accounted for 1–4% of trait variation. These SNPs and haplotypes were located within or adjacent to 38 candidate genes, 21 of which were candidate genes associated with plant tolerance to stresses, including disease resistance. Linkage mapping in four biparental populations to validate GWAS results identified 15 quantitative trait loci (QTL) associated with F. verticillioides resistance. Integration of GWAS and QTL to the maize physical map showed eight colocated loci on chromosomes 2, 3, 4, 5, 9, and 10. QTL on chromosomes 2 and 9 are new. These results reveal that FER resistance is a complex trait that is conditioned by multiple genes with minor effects. The value of selection on identified markers for improving FER resistance is limited; rather, selection to combine small effect resistance alleles combined with genomic selection for polygenic background for both the target and general adaptation traits might be fruitful for increasing FER resistance in maize.
    Electronic ISSN: 2160-1836
    Topics: Biology
    Published by Genetics Society of America (GSA)
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