Microarray profiling of mononuclear peripheral blood cells identifies novle candidate genes related to chemoradiation response in rectal cancer

Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1–2 and downstaging being defined as responders and patients with grade 3–5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced rectal cancer. Moreover, our investigation added further evidence to the importance of mononuclear cells’ mediated response in the neoadjuvant treatment of rectal cancer.This investigation was supported by the Fundación Investigación Biomédica Mutua Madrileña. MC, CC and AB were supported by projects P08-TIC-4299 and CTS2200 of Junta de Andalucía, TIN2009-13489 of DGICT, Madrid, and GREIB PYR_2010-02 and 2010_05 of University of Granada

Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis.

The gene for the atypical NOTCH ligand delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms that function in several developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally inherited chromosome. Here we show that mice that are deficient in Dlk1 have defects in postnatal neurogenesis in the subventricular zone: a developmental continuum that results in depletion of mature neurons in the olfactory bulb. We show that DLK1 is secreted by niche astrocytes, whereas its membrane-bound isoform is present in neural stem cells (NSCs) and is required for the inductive effect of secreted DLK1 on self-renewal. Notably, we find that there is a requirement for Dlk1 to be expressed from both maternally and paternally inherited chromosomes. Selective absence of Dlk1 imprinting in both NSCs and niche astrocytes is associated with postnatal acquisition of DNA methylation at the germ-line-derived imprinting control region. The results emphasize molecular relationships between NSCs and the niche astrocyte cells of the microenvironment, identifying a signalling system encoded by a single gene that functions coordinately in both cell types. The modulation of genomic imprinting in a stem-cell environment adds a new level of epigenetic regulation to the establishment and maintenance of the niche, raising wider questions about the adaptability, function and evolution of imprinting in specific developmental contexts

Expression Profiling of Rectal Tumors Defines Response to Neoadjuvant Treatment Related Genes

To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.C, CC and AB were supported by projects CTS2200 and PI-0710-2013 of Junta de Andalucía, TIN2013-41990-R of Programa Estatal I+D+i MINECO, and GREIB PYR_2010-02 and 2010_05 of University of Granada

Exchange of nutrients and oxygen across the sediment-water interface below a Sparus aurata marine fish farm in the north-western Mediterranean Sea

Purpose: This study analyzes the effects of aquaculture activities in open seawater in the north-western coastal waters of the Mediterranean Sea. It is the first of its kind to be based on benthic flux data gathered in situ below fish farms for this particular area. Materials and methods: Samples were collected on four sampling campaigns over a 1-year cycle under a Sparus aurata fish farm facility where benthic fluxes were measured in situ using light and dark benthic chambers. Bottom water and sediment samples were also collected. Data were compared to those for a nearby control station. Results and discussion: Significant differences were found (ANOVA, p < 0. 05) between concentrations of organic matter (OM), total phosphorus and redox potentials in sediments located under the cages and those of the control station. The consumption of dissolved oxygen (DO) by sediment and positive ammonium (NH4 +) fluxes was stimulated by OM content, with correlations of r = -0. 60 (p < 0. 01) and r = 0. 70 (p < 0. 01), respectively. The OM content of sediments was found to be consistently higher under the cages than at the control station, with the highest value (1. 8 ± 0. 7 %) under the cages observed during the early summer; values of DO and NH4 + fluxes were -64 ± 17 and 12. 7 ± 1. 0 mmol m-2 day-1, respectively. PO4 3- fluxes were consistently higher in the fish farm sediments (between 0. 58 and 0. 98 mmol m-2 day-1) than those observed at the control station. Nitrate (NO3 -) fluxes were found to be consistently negative due to denitrification occurring in the sediments and were related to the concentration of NO3 - in bottom waters (r = 0. 92, p < 0. 01). Si fluxes were shown to be associated with water temperature (r = 0. 59, p < 0. 05). Conclusions: The results imply that sediments located below cages accumulate organic matter originating from aquaculture activities, especially during summer months when this activity increases. Sediments undergo biogeochemical changes that mainly affect fluxes of DO, NH4 + and soluble reactive phosphorus, although these do not seem to have a significant impact on the quality of the water column due to the hydrodynamic characteristics of the area. © 2012 Springer-Verlag.We would like to thank the Caja del Mediterraneo for a predoctoral fellowship fund for this research and Antonio Asuncion Acuigroup Maremar manager for the facilities and support in conducting the study. The translation of this paper was funded by the Universidad Politecnica de Valencia, Spain. We are grateful for the valuable comments of the anonymous reviewers on previous versions of the manuscript.Morata Higón, T.; Sospedra, J.; Falco Giaccaglia, SL.; Rodilla Alama, M. (2012). Exchange of nutrients and oxygen across the sediment-water interface below a Sparus aurata marine fish farm in the north-western Mediterranean Sea. Journal of Soils and Sediments. 12(10):1623-1632. doi:10.1007/s11368-012-0581-2S162316321210APHA, AWWA, and WEF (2005) Standard methods for the examination of water wastewater, 21st edn. American Public Health Association, WashingtonAksu M, Kocatas A (2007) Environmental effects of the three fish farms in Izmir Bay (Aegean Sea-Turkey) on water column and sediment. Rapport du 38e Congrés de la Commission Internationale Pour L’exploration Scientifique de la Mer Méditerranée 38, 414Aminot A, Chaussepied M (1983) Manuel des analyses chimiques en milieu marin. Centre National pour l’Explotation des Oceans, BrestArocena R, Conde D (1999) Sedimento. Métodos en ecología de aguas continentales. Universidad de la República, Montevideo, pp 40–52Asociación Empresarial de Productores de Cultivos Marinas (APROMAR) (2010) La Acuicultura Marina de Peces en España, pp. 69Baumgarten MGZ, Rocha JM, Niencheski LFH (1996) Manual de análises em oceanografia química, Rio GrandeBelias C, Dassenakis M, Scoullos M (2007) Study of the N, P and Si fluxes between fish farm sediment and seawater. Results of simulation experiments employing a benthic chamber under various redox conditions. Mar Chem 103:266–275Berelson WM, McManus J, Coale KH, Johnson KS, Burdige D, Kilgore T, Colodner D, Chavez F, Kudela R, Boucher J (2003) A time series of benthic flux measurements from Monterey Bay, CA. Cont Shelf Res 23:457–481Black KD, McDougall N (2002) Hydrography of four Mediterranean marine cage sites. J Appl Ichthyol 18:129–133Borja A, Rodríguez JG, Black K, Bodoy A, Emblow C, Fernandes TF, Forte J, Karakassis I, Muxika I, Nickell TD, Papageorgiou N, Pranovi F, Sevastou K, Tomassetti P, Angel D (2009) Assessing the suitability of a range of benthic indices in the evaluation of environmental impact of fin and shellfish aquaculture located in sites across Europe. Aquaculture 293:231–240Cermelj B, Ogrinc N, Faganeli J (2001) Anoxic mineralization of biogenic debris in near-shore marine sediments (Gulf of Trieste, northern Adriatic). Sci Total Environ 266:143–152Dell’Anno A, Mei ML, Pusceddu A, Danovaro R (2002) Assessing the trophic state and eutrophication of coastal marine systems: a new approach based on the biochemical composition of sediment organic matter. Mar Pollut Bull 44:611–622Dosdat A (2001) Environmental impact of aquaculture in the Mediterranean: nutritional and feeding aspects. Environmental impact assessment of Mediterranean aquaculture farms. 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A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency. The exchange of energy, gases and particles across the air-sea interface is controlled by a variety of biological, chemical and physical processes that operate across broad spatial and temporal scales. These processes influence the composition, biogeochemical and chemical properties of both the oceanic and atmospheric boundary layers and ultimately shape the Earth system response to climate and environmental change, as detailed in the previous four chapters. In this cross-cutting chapter we present some of the SOLAS achievements over the last decade in terms of integration, upscaling observational information from process-oriented studies and expeditionary research with key tools such as remote sensing and modelling. Here we do not pretend to encompass the entire legacy of SOLAS efforts but rather offer a selective view of some of the major integrative SOLAS studies that combined available pieces of the immense jigsaw puzzle. These include, for instance, COST efforts to build up global climatologies of SOLAS relevant parameters such as dimethyl sulphide, interconnection between volcanic ash and ecosystem response in the eastern subarctic North Pacific, optimal strategy to derive basin-scale CO2 uptake with good precision, or significant reduction of the uncertainties in sea-salt aerosol source functions. Predicting the future trajectory of Earth’s climate and habitability is the main task ahead. Some possible routes for the SOLAS scientific community to reach this overarching goal conclude the chapter

Short-term variability in euphotic zone biogeochemistry and primary productivity at Station ALOHA: A case study of summer 2012

Time-series observations are critical to understand the structure, function, and dynamics of marine ecosystems. The Hawaii Ocean Time-series program has maintained near-monthly sampling at Station ALOHA (22°45′N, 158°00′W) in the oligotrophic North Pacific Subtropical Gyre (NPSG) since 1988 and has identified ecosystem variability over seasonal to interannual timescales. To further extend the temporal resolution of these near-monthly time-series observations, an extensive field campaign was conducted during July–September 2012 at Station ALOHA with near-daily sampling of upper water-column biogeochemistry, phytoplankton abundance, and activity. The resulting data set provided biogeochemical measurements at high temporal resolution and documents two important events at Station ALOHA: (1) a prolonged period of low productivity when net community production in the mixed layer shifted to a net heterotrophic state and (2) detection of a distinct sea-surface salinity minimum feature which was prominent in the upper water column (0–50 m) for a period of approximately 30 days. The shipboard observations during July–September 2012 were supplemented with in situ measurements provided by Seagliders, profiling floats, and remote satellite observations that together revealed the extent of the low productivity and the sea-surface salinity minimum feature in the NPSG.This is the publisher’s final pdf. The article is copyrighted by American Geophysical Union and published by John Wiley & Sons, Inc. It can be found at: http://agupubs.onlinelibrary.wiley.com/agu/journal/10.1002/%28ISSN%291944-9224

Experimental and computational investigations of electron dynamics in micro atmospheric pressure radio-frequency plasma jets operated in He/N2 mixtures

The electron power absorption dynamics in radio frequency driven micro atmospheric pressure capacitive plasma jets are studied based on experimental phase resolved optical emission spectroscopy and the computational particle in cell simulations with Monte Carlo treatment of collisions. The jet is operated at 13.56 MHz in He with different admixture concentrations of N2 and at several driving voltage amplitudes. We find the spatio-temporal dynamics of the light emission of the plasma at various wavelengths to be markedly different. This is understood by revealing the population dynamics of the upper levels of selected emission lines/bands based on comparisons between experimental and simulation results. The populations of these excited states are sensitive to different parts of the electron energy distribution function and to contributions from other excited states. Mode transitions of the electron power absorption dynamics from the Ω- to the Penning-mode are found to be induced by changing the N2 admixture concentration and the driving voltage amplitude. Our numerical simulations reveal details of this mode transition and provide novel insights into the operation details of the Penning-mode. The characteristic excitation/emission maximum at the time of maximum sheath voltage at each electrode is found to be based on two mechanisms: (i) a direct channel, i.e. excitation/emission caused by electrons generated by Penning ionization inside the sheaths and (ii) an indirect channel, i.e. secondary electrons emitted from the electrode due to the impact of positive ions generated by Penning ionization at the electrodes

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access