Differences on the level of hepatic transcriptome between two flatfish species in response to liver cancer and environmental pollution levels

Environmental factors can cause cancer in both wild animals and humans. In ecological settings, genetic variation and natural selection can sometimes produce resilience to the negative impacts of environmental change. An increase in oncogenic substances in natural habitats has therefore, unintentionally, created opportunities for using polluted habitats to study cancer defence mechanisms. The Baltic and North Sea are among the most contaminated marine areas, with a long history of pollution. Two flatfish species (flounder, Platichthys flesus and dab, Limanda limanda) are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is more prevalent in dab, suggesting species-specific differences in vulnerability and/or defence mechanisms. We conducted gene expression analyses for 30 flatfishes. We characterize between- and within-species patterns in potential cancer-related mechanisms. By comparing cancerous and healthy fishes, and noncancerous fishes from clean and polluted sites, we suggest also genes and related physiological mechanisms that could contribute to a higher resistance to pollution-induced cancer in flounders. We discovered changes in transcriptome related to elevated pollutant metabolism, alongside greater tumour suppression mechanisms in the liver tissue of flounders compared to dabs. This suggests either hormetic upregulation of tumour suppression or a stronger natural selection pressure for higher cancer resistance for flounders in polluted environment. Based on gene expression patterns seen in cancerous and healthy fish, for liver cancer to develop in flounders, genetic defence mechanisms need to be suppressed, while in dabs, analogous process is weak or absent. We conclude that wild species could offer novel insights and ideas for understanding the nature and evolution of natural cancer defence mechanisms.We are grateful to the crew of RW Walther Herwig III for all-round help during the fieldwork. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 951963.We are grateful to the crew of RW Walther Herwig III for all-round help during the fieldwork. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 951963

A New Window of Exploration in the Mass Spectrum: Strong Lensing by Galaxy Groups in the SL2S

The existence of strong lensing systems with Einstein radii (Re) covering the full mass spectrum, from ~1-2" (produced by galaxy scale dark matter haloes) to >10" (produced by galaxy cluster scale haloes) have long been predicted. Many lenses with Re around 1-2" and above 10" have been reported but very few in between. In this article, we present a sample of 13 strong lensing systems with Re in the range 3"- 8", i.e. systems produced by galaxy group scale dark matter haloes, spanning a redshift range from 0.3 to 0.8. This opens a new window of exploration in the mass spectrum, around 10^{13}- 10^{14} M_{sun}, which is a crucial range for understanding the transition between galaxies and galaxy clusters. Our analysis is based on multi-colour CFHTLS images complemented with HST imaging and ground based spectroscopy. Large scale properties are derived from both the light distribution of the elliptical galaxies group members and weak lensing of the faint background galaxy population. On small scales, the strong lensing analysis yields Einstein radii between 2.5" and 8". On larger scales, the strong lenses coincide with the peak of the light distribution, suggesting that mass is traced by light. Most of the luminosity maps have complicated shapes, indicating that these intermediate mass structures are dynamically young. Fitting the reduced shear with a Singular Isothermal Sphere, we find sigma ~ 500 km/s and an upper limit of ~900 km/s for the whole sample. The mass to light ratio for the sample is found to be M/L_i ~ 250 (solar units, corrected for evolution), with an upper limit of 500. This can be compared to mass to light ratios of small groups (with sigma ~ 300 km/s and galaxy clusters with sigma > 1000 km/s, thus bridging the gap between these mass scales.Comment: A&A Accepted. Draft with Appendix images can be found at http://www.dark-cosmology.dk/~marceau/groups_sl2s.pd

New Insights in the Contribution of Voltage-Gated Nav Channels to Rat Aorta Contraction

BACKGROUND: Despite increasing evidence for the presence of voltage-gated Na(+) channels (Na(v)) isoforms and measurements of Na(v) channel currents with the patch-clamp technique in arterial myocytes, no information is available to date as to whether or not Na(v) channels play a functional role in arteries. The aim of the present work was to look for a physiological role of Na(v) channels in the control of rat aortic contraction. METHODOLOGY/PRINCIPAL FINDINGS: Na(v) channels were detected in the aortic media by Western blot analysis and double immunofluorescence labeling for Na(v) channels and smooth muscle alpha-actin using specific antibodies. In parallel, using real time RT-PCR, we identified three Na(v) transcripts: Na(v)1.2, Na(v)1.3, and Na(v)1.5. Only the Na(v)1.2 isoform was found in the intact media and in freshly isolated myocytes excluding contamination by other cell types. Using the specific Na(v) channel agonist veratridine and antagonist tetrodotoxin (TTX), we unmasked a contribution of these channels in the response to the depolarizing agent KCl on rat aortic isometric tension recorded from endothelium-denuded aortic rings. Experimental conditions excluded a contribution of Na(v) channels from the perivascular sympathetic nerve terminals. Addition of low concentrations of KCl (2-10 mM), which induced moderate membrane depolarization (e.g., from -55.9+/-1.4 mV to -45.9+/-1.2 mV at 10 mmol/L as measured with microelectrodes), triggered a contraction potentiated by veratridine (100 microM) and blocked by TTX (1 microM). KB-R7943, an inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger, mimicked the effect of TTX and had no additive effect in presence of TTX. CONCLUSIONS/SIGNIFICANCE: These results define a new role for Na(v) channels in arterial physiology, and suggest that the TTX-sensitive Na(v)1.2 isoform, together with the Na(+)/Ca(2+) exchanger, contributes to the contractile response of aortic myocytes at physiological range of membrane depolarization

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

Gravitational Lensing

Gravitational lensing has developed into one of the most powerful tools for the analysis of the dark universe. This review summarises the theory of gravitational lensing, its main current applications and representative results achieved so far. It has two parts. In the first, starting from the equation of geodesic deviation, the equations of thin and extended gravitational lensing are derived. In the second, gravitational lensing by stars and planets, galaxies, galaxy clusters and large-scale structures is discussed and summarised.Comment: Invited review article to appear in Classical and Quantum Gravity, 85 pages, 15 figure

Pulse Jet Mixer Overblow Testing for Assessment of Loadings During Multiple Overblows

The U.S. Department of Energy (DOE) Office of River Protection’s Waste Treatment Plant (WTP) is being designed and built to pretreat and then vitrify a large portion of the wastes in Hanford’s 177 underground waste storage tanks. The WTP consists of three primary facilities: pretreatment, low-activity waste (LAW) vitrification, and high-level waste (HLW) vitrification. The pretreatment facility will receive waste feed from the Hanford tank farms and separate it into 1) a high-volume, low-activity liquid stream stripped of most solids and radionuclides and 2) a much smaller volume of HLW slurry containing most of the solids and most of the radioactivity. Many of the vessels in the pretreatment facility will contain pulse jet mixers (PJMs) that will provide some or all of the mixing in the vessels. This technology was selected for use in so-called “black cell” regions of the WTP, where maintenance capability will not be available for the operating life of the WTP. PJM technology was selected for use in these regions because it has no moving mechanical parts that require maintenance. The vessels with the most concentrated slurries will also be mixed with air spargers and/or steady jets in addition to the mixing provided by the PJMs. This report contains the results of single and multiple PJM overblow tests conducted in a large, ~13 ft-diameter × 15-ft-tall tank located in the high bay of the Pacific Northwest National Laboratory (PNNL) 336 Building test facility. These single and multiple PJM overblow tests were conducted using water and a clay simulant to bound the lower and upper rheological properties of the waste streams anticipated to be processed in the WTP. Hydrodynamic pressures were measured at a number of locations in the test vessel using an array of nine pressure sensors and four hydrophones. These measurements were made under normal and limiting vessel operating conditions (i.e., maximum PJM fluid emptying velocity, maximum and minimum vessel contents for PJM operation, and maximum and minimum rheological properties). Test data collected from the PJM overblow tests were provided to Bechtel National, Inc. (BNI) for assessing hydrostatic, dynamic, and acoustic pressure loadings on in-tank structures during 1) single overblows; 2) multiple overlapping overblows of two to four PJMs; 3) simultaneous overblows of pairs of PJMs

Temporal-spatial profiling of pedunculopontine galanin-cholinergic neurons in the lactacystin rat model of Parkinson’s disease

Parkinson’s disease (PD) is conventionally seen as resulting from single-system neurodegeneration affecting nigrostriatal dopaminergic neurons. However, accumulating evidence indicates a multi-system degeneration and neurotransmitter deficiencies, including cholinergic neurons which degenerate in a brainstem nucleus, the pedunculopontine nucleus (PPN), resulting in motor- and cognitive impairments. The neuropeptide galanin can inhibit cholinergic transmission, whilst being upregulated in degenerating brain regions associated with cognitive decline. Here we determined the temporal-spatial profile of progressive expression of endogenous galanin within degenerating cholinergic neurons, across the rostro-caudal axis of the PPN, by utilising the lactacystin-induced rat model of PD. First, we show progressive neuronal death affecting nigral dopaminergic and PPN cholinergic neurons, reflecting that seen in PD patients, to facilitate use of this model for assessing the therapeutic potential of bioactive peptides. Next, stereological analyses of the lesioned brain hemisphere found that the number of PPN cholinergic neurons expressing galanin increased by 11%, compared to sham-lesioned controls, increasing by a further 5% as the neurodegenerative process evolved. Galanin upregulation within cholinergic PPN neurons was most prevalent closest to the intra-nigral lesion site, suggesting that galanin upregulation in such neurons adapt intrinsically to neurodegeneration, to possibly neuroprotect. This is the first report on the extent and pattern of galanin expression in cholinergic neurons across distinct PPN subregions in both the intact rat CNS and lactacystin lesioned rats. The findings pave the way for future work to target galanin signaling in the PPN, to determine the extent to which upregulated galanin expression could offer a viable treatment strategy for ameliorating PD symptoms associated with cholinergic degeneration

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research