84 research outputs found

    Seagrass Canopy Photosynthetic Response Is a Function of Canopy Density and Light Environment: A Model for Amphibolis griffithii

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    A three-dimensional computer model of canopies of the seagrass Amphibolis griffithii was used to investigate the consequences of variations in canopy structure and benthic light environment on leaf-level photosynthetic saturation state. The model was constructed using empirical data of plant morphometrics from a previously conducted shading experiment and validated well to in-situ data on light attenuation in canopies of different densities. Using published values of the leaf-level saturating irradiance for photosynthesis, results show that the interaction of canopy density and canopy-scale photosynthetic response is complex and non-linear, due to the combination of self-shading and the non-linearity of photosynthesis versus irradiance (P-I) curves near saturating irradiance. Therefore studies of light limitation in seagrasses should consider variation in canopy structure and density. Based on empirical work, we propose a number of possible measures for canopy scale photosynthetic response that can be plotted to yield isoclines in the space of canopy density and light environment. These plots can be used to interpret the significance of canopy changes induced as a response to decreases in the benthic light environment: in some cases canopy thinning can lead to an equivalent leaf level light environment, in others physiological changes may also be required but these alone may be inadequate for canopy survival. By providing insight to these processes the methods developed here could be a valuable management tool for seagrass conservation during dredging or other coastal developments

    Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case–control study

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    Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy.A case-control study was performed to determine the prognostic value of DNA ploidy and p53 in IBD-related neoplasia. Cases with IBD-related colorectal cancer (CRC), detected in our surveillance program between 1985-2008, were selected and matched with two controls, for age, gender, disease characteristics, interval of follow-up, PSC, and previous surgery. Biopsies were assessed for DNA ploidy, p53, grade of inflammation and neoplasia. Progression to neoplasia was analyzed with Cox regression analysis, adjusting for potentially confounding variables.Adjusting for age, we found statistically significant Hazard ratios (HR) between development of CRC, and low grade dysplasia (HR5.5; 95%CI 2.6-11.5), abnormal DNA ploidy (DNA index (DI) 1.06-1.34, HR4.7; 95%CI 2.9-7.8 and DI>1.34, HR6.6; 95%CI 3.7-11.7) and p53 immunopositivity (HR3.0; 95%CI 1.9-4.7) over time. When adjusting for all confounders, abnormal DNA ploidy (DI 1.06-1.34, HR4.7; 95%CI 2.7-7.9 and DI>1.34, HR5.0; 95%CI 2.5-10.0) and p53 immunopositivity (HR1.7; 95%CI 1.0-3.1) remained statistically significant predictive of neoplasia. In longstanding IBD, abnormal DNA ploidy and p53 immunopositivity are important risk factors of developing CRC. The yield of surveillance may potentially increase by adding these biomarkers to the routine assessment of biopsies

    Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells

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    Recently, we demonstrated that sigma-2 receptors may have the potential to be a biomarker of tumour cell proliferation (Mach et al (1997) Cancer Res57: 156–161). If sigma-2 receptors were a biomarker of tumour cell proliferation, they would be amenable to detection by non-invasive imaging procedures, thus eliminating many of the problems associated with the flow cytometric measures of tumour cell proliferation presently used in the clinic. To be a good biomarker of tumour cell proliferation, the expression of sigma-2 receptors must be essentially independent of many of the biological, physiological, and/or environmental properties that are found in solid tumours. In the investigation reported here, the mouse mammary adenocarcinoma lines, 66 (diploid) and 67 (aneuploid), 9L rat brain tumour cells, and MCF-7 human breast tumour cells were used to study the extent and kinetics of expression of sigma-2 receptors in proliferative (P) and quiescent (Q) tumour cells as a function of species, cell type, ploidy, pH, nutrient depletion, metabolic state, recruitment from the Q-cell compartment to the P-cell compartment, and treatment with tamoxifen. In these experiments, the expression of sigma-2 receptors solely reflected the proliferative status of the tumour cells. None of the biological, physiological, or environmental properties that were investigated had a measurable effect on the expression of sigma-2 receptors in these model systems. Consequently, these data suggest that the proliferative status of tumours and normal tissues can be non-invasively assessed using radiolabelled ligands that selectively bind sigma-2 receptors. © 1999 Cancer Research Campaig

    Externalizing behavior in early childhood and body mass index from age 2 to 12 years: longitudinal analyses of a prospective cohort study

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    Background: Some evidence suggests that obesity and behavior problems are related in children, but studies have been conflicting and have rarely included children under age 4. An association between behavior problems in early childhood and risk for obesity could suggest that a common set of factors contribute to both. Our research objectives were to determine the extent to which externalizing behavior in early childhood is related to body mass index (BMI) in early childhood and through age 12, and to evaluate whether these associations differ by sex and race. Methods: Data from the NICHD Study of Early Child Care and Youth Development were analyzed. Externalizing behaviors at 24 months were assessed by mothers using the Child Behavior Checklist. BMI was calculated from measured height and weight assessed 7 times between age 2 and 12 years. Linear mixed effects models were used to assess associations between 24 month externalizing behavior and BMI from 2 to 12 years, calculate predicted differences in BMI, and evaluate effect modification. Results: Externalizing behavior at 24 months was associated with a higher BMI at 24 months and through age 12. Results from a linear mixed effects model, controlling for confounding variables and internalizing behavior, predicted a difference in BMI of approximately 3/4 of a unit at 24 months of age comparing children with high levels of externalizing behavior to children with low levels of externalizing behavior. There was some evidence of effect modification by race; among white children, the average BMI difference remained stable through age 12, but it doubled to 1.5 BMI units among children who were black or another race. Conclusions: Our analyses suggest that externalizing behaviors in early childhood are associated with children's weight status early in childhood and throughout the elementary school years, though the magnitude of the effect is modest.https://doi.org/10.1186/1471-2431-10-4

    RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

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    Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers

    Prioritizing Land and Sea Conservation Investments to Protect Coral Reefs

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    Background: Coral reefs have exceptional biodiversity, support the livelihoods of millions of people, and are threatened by multiple human activities on land (e.g. farming) and in the sea (e.g. overfishing). Most conservation efforts occur at local scales and, when effective, can increase the resilience of coral reefs to global threats such as climate change (e.g. warming water and ocean acidification). Limited resources for conservation require that we efficiently prioritize where and how to best sustain coral reef ecosystems

    Physical fitness in morbidly obese patients: effect of gastric bypass surgery and exercise training

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    Background There is a growing consensus that bariatric surgery is currently the most efficacious and long-term treatment for clinically severe obesity. However, it remains to be determined whether poor physical fitness, an important characteristic of these patients, improves as well. The purpose of this pilot study is to investigate the effect of gastric bypass surgery on physical fitness and to determine if an exercise program in the first 4 months is beneficial. Methods Fifteen morbidly obese patients (BMI 43.0 kg/m(2)) were tested before and 4 months after gastric bypass surgery. Eight of them followed a combined endurance and strength training program. Before and after 4 months the operation, anthropometrical characteristics were measured, and an extensive assessment of physical fitness (strength, aerobic, and functional capacity) was performed. Results Large-scale weight loss through gastric bypass surgery results in a decrease in dynamic and static muscle strength and no improvement of aerobic capacity. In contrast, an intensive exercise program could prevent the decrease and even induced an increase in strength of most muscle groups. Together with an improvement in aerobic capacity, functional capacity increased significantly. Both groups evolved equally with regard to body composition (decrease in fat mass and fat-free mass). Conclusions An exercise training program in the first 4 months after bariatric surgery is effective and should be promoted, considering the fact that physical fitness does not improve by weight loss only

    Acanthaster planci Outbreak: Decline in Coral Health, Coral Size Structure Modification and Consequences for Obligate Decapod Assemblages

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    Although benthic motile invertebrate communities encompass the vast majority of coral reef diversity, their response to habitat modification has been poorly studied. A variety of benthic species, particularly decapods, provide benefits to their coral host enabling them to cope with environmental stressors, and as a result benefit the overall diversity of coral-associated species. However, little is known about how invertebrate assemblages associated with corals will be affected by global perturbations, (either directly or indirectly via their coral host) or their consequences for ecosystem resilience. Analysis of a ten year dataset reveals that the greatest perturbation at Moorea over this time was an outbreak of the corallivorous sea star Acanthaster planci from 2006 to 2009 impacting habitat health, availability and size structure of Pocillopora spp. populations and highlights a positive relationship between coral head size and survival. We then present the results of a mensurative study in 2009 conducted at the end of the perturbation (A. planci outbreak) describing how coral-decapod communities change with percent coral mortality for a selected coral species, Pocillopora eydouxi. The loss of coral tissue as a consequence of A. planci consumption led to an increase in rarefied total species diversity, but caused drastic modifications in community composition driven by a shift from coral obligate to non-obligate decapod species. Our study highlights that larger corals left with live tissue in 2009, formed a restricted habitat where coral obligate decapods, including mutualists, could subsist. We conclude that the size structure of Pocillopora populations at the time of an A. planci outbreak may greatly condition the magnitude of coral mortality as well as the persistence of local populations of obligate decapods

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
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