Practical measures for improving the ecological state of lake Marken using in depth system knowledge

For Lake Marken in the Netherlands, high suspended sediment concentrations result in reduced ecological values and prevent goals and standards from being met (Water Framework Directive, Natura 2000). A practical measure to improve the ecology that is currently studied is the construction of sheltered areas in the North West part of Lake Marken. For implementation of this measure, a strategy is being followed that combines in depth system knowledge with stakeholder aspects. In the present paper we will show which knowledge of the underlying physical and ecological processes was needed and how it was applied in the strategy. We used a coupled silt model for Lake Marken to study effects of the structures on hydrodynamics, waves, and sediment. Results of the silt model simulations were interpreted with in depth ecological expert knowledge to assess the ecological impact of the structures. Effects of the considered sheltered areas on transparency and wave- and siltdynamics are limited compared to the scale of the lake. However, these changes give local opportunities for ecology. Its effectiveness may be enhanced by local un-deepening

Natuurlijk IJsselmeer: ecodynamisch visie IJsselmeer 2100

Deze ecodynamische visie laat een palet van potentiële ontwikkelingen voor het IJsselmeer zien: ecodynamische ontwikkelingen, die bijdragen aan meerdere functies en ambities waaronder natuur, waterveiligheid, visserij, recreatie en infrastructuur, en waarbij optimaal gebruik wordt gemaakt van de in het gebied aanwezige natuurlijke factoren als wind, water, sediment en vegetatie. Deze visie laat zien dat er kansen liggen voor nieuwe vormen van waterbouw, die de veiligheid van de Houtribdijk en de Afsluitdijk vergroten. Ook worden de kansen in kaart gebracht om met moerassen zowel de waterveiligheid als de biodiversiteit langs dijken bij de Noordoostpolder te verbeteren

Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

<p>Abstract</p> <p>Background</p> <p>Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (<it>DPYD</it>).</p> <p>Methods</p> <p>In this study, we evaluated <it>DPYD </it>promoter methylation through quantitative methylation-specific PCR and screened <it>DPYD </it>for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. <it>DPYD </it>promoter methylation was also assessed in tumor tissue from 29 patients</p> <p>Results</p> <p>Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, <it>DPYD </it>promoter methylation and large <it>DPYD </it>intragenic rearrangements were absent in all cases analyzed.</p> <p>Conclusions</p> <p>Our results indicate that <it>DPYD </it>promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.</p

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

<p>Abstract</p> <p>Background</p> <p>Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.</p> <p>Methods</p> <p>Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis.</p> <p>Results</p> <p>In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis.</p> <p>Conclusion</p> <p>Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy.</p

Analysis of Polymorphisms and Haplotype Structure of the Human Thymidylate Synthase Genetic Region: A Tool for Pharmacogenetic Studies

5-fluorouracil (5FU), a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms). Prior studies implicated a VNTR (variable numbers of tandem repeats) polymorphism in the 5′-untranslated region (5′-UTR) of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T) repeats and novel single nucleotide polymorphisms (SNPs) flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt), polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing

Long-term population dynamics of dreissenid mussels (Dreissena polymorpha and D. rostriformis): a cross-system analysis

Dreissenid mussels (including the zebra mussel Dreissena polymorpha and the quagga mussel D. rostriformis) are among the world's most notorious invasive species, with large and widespread ecological and economic effects. However, their long-term population dynamics are poorly known, even though these dynamics are critical to determining impacts and effective management. We gathered and analyzed 67 long-term (>10 yr) data sets on dreissenid populations from lakes and rivers across Europe and North America. We addressed five questions: (1) How do Dreissena populations change through time? (2) Specifically, do Dreissena populations decline substantially after an initial outbreak phase? (3) Do different measures of population performance (biomass or density of settled animals, veliger density, recruitment of young) follow the same patterns through time? (4) How do the numbers or biomass of zebra mussels or of both species combined change after the quagga mussel arrives? (5) How does body size change over time? We also considered whether current data on long-term dynamics of Dreissena populations are adequate for science and management. Individual Dreissena populations showed a wide range of temporal dynamics, but we could detect only two general patterns that applied across many populations: (1) Populations of both species increased rapidly in the first 1–2 yr after appearance, and (2) quagga mussels appeared later than zebra mussels and usually quickly caused large declines in zebra mussel populations. We found little evidence that combined Dreissena populations declined over the long term. Different measures of population performance were not congruent; the temporal dynamics of one life stage or population attribute cannot generally be accurately inferred from the dynamics of another. We found no consistent patterns in the long-term dynamics of body size. The long-term dynamics of Dreissena populations probably are driven by the ecological characteristics (e.g., predation, nutrient inputs, water temperature) and their temporal changes at individual sites rather than following a generalized time course that applies across many sites. Existing long-term data sets on dreissenid populations, although clearly valuable, are inadequate to meet research and management needs. Data sets could be improved by standardizing sampling designs and methods, routinely collecting more variables, and increasing support.Deutsche Forschungsgemeinschaft Cary Institute of Ecosystem Studies (DLS) NSF‐LTREB. Grant Number: DEB‐1556246 NSF‐OPUS. Grant Numbers: DEB‐1456532, JE 288/9‐1, JE 288/9‐2, TÁMOP‐4.2.2.A‐11/1/KONV‐2012‐0038, GINOP‐2.3.2‐15‐2016‐00019, LG‐T; USGS G14AC000263, US EPA GL00E01184 Cornell Agricultural Experiment Station. Grant Number: NYC‐0226747 New York State Department of Environmental Conservation. Grant Number: 1517823 Belarusian Republican Foundation for Fundamental Researc