Inorganic arsenic causes apoptosis cell death and immunotoxicity on European sea bass (Dicentrarchus labrax)

Inorganic arsenic (As) is one of the most toxic pollutants in the water. We have studied their effects on the marine teleost European sea bass (Dicentrarchus labrax) at 2 and 10 days of 5 μMofAs2O3 (sub-lethal doses) waterborne exposure. Arsenic accumulates in liver and gill tissues. The expression profile of five genes (bax, blc2, casp3, casp8 and casp9) involved in apoptosis cell death confirmed apoptotic effects in liver, slight changes in gill and no effects in skin according with the histopathology findings. Total IgM level and peroxidase activities were increased at 2 and 10 days, respectively. The bactericidal activity was decreased at 2 days after As exposure. A general decrease of cellular immune activities with significant differences in the case of respiratory burst activity was observed after 2 and 10 days of exposure. This work describes for the first time the effects of As exposure on European sea bass.Versión del editor2,35

PET tracers for clinical imaging of breast cancer

Molecular imaging of breast cancer has undoubtedly permitted a substantial development of the overall diagnostic accuracy of this malignancy in the last years. Accurate tumour staging, design of individually suited therapies, response evaluation, early detection of recurrence and distant lesions have also evolved in parallel with the development of novel molecular imaging approaches. In this context, positron emission tomography (PET) can be probably seen as the most interesting molecular imaging technology with straightforward clinical application for such purposes. Dozens of radiotracers for PET imaging of breast cancer have been tested in laboratory animals. However, in this review we shall focus mainly in the smaller group of PET radiopharmaceuticals that have lead through into the clinical setting. PET imaging can be used to target general metabolic phenomena related to tumoural transformation, including glucose metabolism and cell proliferation, but can also be directed to specific hormone receptors that are characteristic of the breast cancer cell. Many other receptors and transport molecules present in the tumour cells could also be of interest for imaging. Furthermore, molecules related with the tumour microenvironment, tumour induced angiogenesis or even hypoxia could also be used as molecular biomarkers for breast cancer imaging

IEOOS: the Spanish Institute of Oceanography Observing System

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Characterization of protons accelerated from a 3 TW table-top laser system

[EN] We report on benchmark tests of a 3 TW/50 fs, table-top laser system specifically developed for proton acceleration with an intrinsic pump rate up to 100 Hz. In two series of single-shot measurements differing in pulse energy and contrast the successful operation of the diode pumped laser is demonstrated. Protons have been accelerated up to 1.6 MeV in interactions of laser pulses focused on aluminium and mylar foils between 0.8 and 25 mu m thickness. Their spectral distributions and maximum energies are consistent with former experiments under similar conditions. These results show the suitability of our system and provide a reference for studies of laser targets at high repetition rate and possible applications.This project has been funded by Centro para el Desarrollo Tecnologico Industrial (CDTI, Spain) within the INNPRONTA program, grant no. IPT-20111027, by EUROSTARS project E9113, and by the Spanish Ministry for Economy and Competitiveness within the Retos-Colaboracion 2015 initiative, ref. RTC-2015-3278-1.Bellido-Millán, PJ.; Lera, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Torres Peiró, S.; Galán, M.; Mur, P.... (2017). Characterization of protons accelerated from a 3 TW table-top laser system. Journal of Instrumentation. 12:1-12. https://doi.org/10.1088/1748-0221/12/05/T05001S11212Daido, H., Nishiuchi, M., & Pirozhkov, A. S. (2012). Review of laser-driven ion sources and their applications. Reports on Progress in Physics, 75(5), 056401. doi:10.1088/0034-4885/75/5/056401Macchi, A., Borghesi, M., & Passoni, M. (2013). Ion acceleration by superintense laser-plasma interaction. Reviews of Modern Physics, 85(2), 751-793. doi:10.1103/revmodphys.85.751Ledingham, K., Bolton, P., Shikazono, N., & Ma, C.-M. (2014). Towards Laser Driven Hadron Cancer Radiotherapy: A Review of Progress. Applied Sciences, 4(3), 402-443. doi:10.3390/app4030402Kraft, S. D., Richter, C., Zeil, K., Baumann, M., Beyreuther, E., Bock, S., … Pawelke, J. (2010). Dose-dependent biological damage of tumour cells by laser-accelerated proton beams. New Journal of Physics, 12(8), 085003. doi:10.1088/1367-2630/12/8/085003Yogo, A., Sato, K., Nishikino, M., Mori, M., Teshima, T., Numasaki, H., … Daido, H. (2009). Application of laser-accelerated protons to the demonstration of DNA double-strand breaks in human cancer cells. Applied Physics Letters, 94(18), 181502. doi:10.1063/1.3126452Fritzler, S., Malka, V., Grillon, G., Rousseau, J. P., Burgy, F., Lefebvre, E., … Ledingham, K. W. D. (2003). Proton beams generated with high-intensity lasers: Applications to medical isotope production. Applied Physics Letters, 83(15), 3039-3041. doi:10.1063/1.1616661Kishimura, H., Morishita, H., Okano, Y. H., Okano, Y., Hironaka, Y., Kondo, K., … Nemoto, K. (2004). Enhanced generation of fast protons from a polymer-coated metal foil by a femtosecond intense laser field. Applied Physics Letters, 85(14), 2736-2738. doi:10.1063/1.1803915Nakamura, S., Iwashita, Y., Noda, A., Shirai, T., Tongu, H., Fukumi, A., … Wada, Y. (2006). Real-Time Optimization of Proton Production by Intense Short-Pulse Laser with Time-of-Flight Measurement. Japanese Journal of Applied Physics, 45(No. 34), L913-L916. doi:10.1143/jjap.45.l913Nishiuchi, M., Fukumi, A., Daido, H., Li, Z., Sagisaka, A., Ogura, K., … Nakamura, S. (2006). The laser proton acceleration in the strong charge separation regime. Physics Letters A, 357(4-5), 339-344. doi:10.1016/j.physleta.2006.04.053Yogo, A., Daido, H., Fukumi, A., Li, Z., Ogura, K., Sagisaka, A., … Itoh, A. (2007). Laser prepulse dependency of proton-energy distributions in ultraintense laser-foil interactions with an online time-of-flight technique. Physics of Plasmas, 14(4), 043104. doi:10.1063/1.2721066Robinson, A. P. L., Foster, P., Adams, D., Carroll, D. C., Dromey, B., Hawkes, S., … Neely, D. (2009). Spectral modification of laser-accelerated proton beams by self-generated magnetic fields. New Journal of Physics, 11(8), 083018. doi:10.1088/1367-2630/11/8/083018Nemoto, K., Maksimchuk, A., Banerjee, S., Flippo, K., Mourou, G., Umstadter, D., & Bychenkov, V. Y. (2001). Laser-triggered ion acceleration and table top isotope production. Applied Physics Letters, 78(5), 595-597. doi:10.1063/1.1343845Lee, K., Park, S. H., Cha, Y.-H., Lee, J. Y., Lee, Y. W., Yea, K.-H., & Jeong, Y. U. (2008). Generation of intense proton beams from plastic targets irradiated by an ultraintense laser pulse. Physical Review E, 78(5). doi:10.1103/physreve.78.056403Yogo, A., Daido, H., Bulanov, S. V., Nemoto, K., Oishi, Y., Nayuki, T., … Tajima, T. (2008). Laser ion acceleration via control of the near-critical density target. Physical Review E, 77(1). doi:10.1103/physreve.77.016401Lee, K., Lee, J. Y., Park, S. H., Cha, Y.-H., Lee, Y. W., Kim, K. N., & Jeong, Y. U. (2011). Dominant front-side acceleration of energetic proton beams from plastic targets irradiated by an ultraintense laser pulse. Physics of Plasmas, 18(1), 013101. doi:10.1063/1.3496058OKIHARA, S., SENTOKU, Y., SUEDA, K., SHIMIZU, S., SATO, F., MIYANAGA, N., … SAKABE, S. (2002). Energetic Proton Generation in a Thin Plastic Foil Irradiated by Intense Femtosecond Lasers. Journal of Nuclear Science and Technology, 39(1), 1-5. doi:10.1080/18811248.2002.9715150McKenna, P., Ledingham, K. W. D., Spencer, I., McCany, T., Singhal, R. P., Ziener, C., … Clark, E. L. (2002). Characterization of multiterawatt laser-solid interactions for proton acceleration. Review of Scientific Instruments, 73(12), 4176-4184. doi:10.1063/1.1516855Spencer, I., Ledingham, K. W. D., McKenna, P., McCanny, T., Singhal, R. P., Foster, P. S., … Davies, J. R. (2003). Experimental study of proton emission from 60-fs, 200-mJ high-repetition-rate tabletop-laser pulses interacting with solid targets. Physical Review E, 67(4). doi:10.1103/physreve.67.046402Kaluza, M., Schreiber, J., Santala, M. I. K., Tsakiris, G. D., Eidmann, K., Meyer-ter-Vehn, J., & Witte, K. J. (2004). Influence of the Laser Prepulse on Proton Acceleration in Thin-Foil Experiments. Physical Review Letters, 93(4). doi:10.1103/physrevlett.93.045003Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.185002Neely, D., Foster, P., Robinson, A., Lindau, F., Lundh, O., Persson, A., … McKenna, P. (2006). Enhanced proton beams from ultrathin targets driven by high contrast laser pulses. Applied Physics Letters, 89(2), 021502. doi:10.1063/1.2220011Steinke, S., Henig, A., Schnürer, M., Sokollik, T., Nickles, P. V., Jung, D., … Habs, D. (2010). Efficient ion acceleration by collective laser-driven electron dynamics with ultra-thin foil targets. Laser and Particle Beams, 28(1), 215-221. doi:10.1017/s0263034610000157Strickland, D., & Mourou, G. (1985). Compression of amplified chirped optical pulses. Optics Communications, 56(3), 219-221. doi:10.1016/0030-4018(85)90120-8Yogo, A., Kondo, K., Mori, M., Kiriyama, H., Ogura, K., Shimomura, T., … Bolton, P. R. (2014). Insertable pulse cleaning module with a saturable absorber pair and a compensating amplifier for high-intensity ultrashort-pulse lasers. Optics Express, 22(2), 2060. doi:10.1364/oe.22.002060Trisorio, A., Grabielle, S., Divall, M., Forget, N., & Hauri, C. P. (2012). Self-referenced spectral interferometry for ultrashort infrared pulse characterization. Optics Letters, 37(14), 2892. doi:10.1364/ol.37.002892Seimetz, M., Bellido, P., Soriano, A., Garcia Lopez, J., Jimenez-Ramos, M. C., Fernandez, B., … Benlloch, J. M. (2015). Calibration and Performance Tests of Detectors for Laser-Accelerated Protons. IEEE Transactions on Nuclear Science, 62(6), 3216-3224. doi:10.1109/tns.2015.2480682Nürnberg, F., Schollmeier, M., Brambrink, E., Blažević, A., Carroll, D. C., Flippo, K., … Roth, M. (2009). Radiochromic film imaging spectroscopy of laser-accelerated proton beams. Review of Scientific Instruments, 80(3), 033301. doi:10.1063/1.3086424Oishi, Y., Nayuki, T., Fujii, T., Takizawa, Y., Wang, X., Yamazaki, T., … Andreev, A. A. (2005). Dependence on laser intensity and pulse duration in proton acceleration by irradiation of ultrashort laser pulses on a Cu foil target. Physics of Plasmas, 12(7), 073102. doi:10.1063/1.1943436Nishiuchi, M., Daito, I., Ikegami, M., Daido, H., Mori, M., Orimo, S., … Yoshiyuki, T. (2009). Focusing and spectral enhancement of a repetition-rated, laser-driven, divergent multi-MeV proton beam using permanent quadrupole magnets. Applied Physics Letters, 94(6), 061107. doi:10.1063/1.3078291Antici, P., Fuchs, J., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Pépin, H. (2007). Energetic protons generated by ultrahigh contrast laser pulses interacting with ultrathin targets. Physics of Plasmas, 14(3), 030701. doi:10.1063/1.2480610Green, J. S., Carroll, D. C., Brenner, C., Dromey, B., Foster, P. S., Kar, S., … Zepf, M. (2010). Enhanced proton flux in the MeV range by defocused laser irradiation. New Journal of Physics, 12(8), 085012. doi:10.1088/1367-2630/12/8/085012Zeil, K., Kraft, S. D., Bock, S., Bussmann, M., Cowan, T. E., Kluge, T., … Schramm, U. (2010). The scaling of proton energies in ultrashort pulse laser plasma acceleration. New Journal of Physics, 12(4), 045015. doi:10.1088/1367-2630/12/4/045015Nishiuchi, M., Daido, H., Yogo, A., Orimo, S., Ogura, K., Ma, J., … Azuma, H. (2008). Efficient production of a collimated MeV proton beam from a polyimide target driven by an intense femtosecond laser pulse. Physics of Plasmas, 15(5), 053104. doi:10.1063/1.2928161Macchi, A., Sgattoni, A., Sinigardi, S., Borghesi, M., & Passoni, M. (2013). Advanced strategies for ion acceleration using high-power lasers. Plasma Physics and Controlled Fusion, 55(12), 124020. doi:10.1088/0741-3335/55/12/124020Fuchs, J., Antici, P., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Audebert, P. (2005). Laser-driven proton scaling laws and new paths towards energy increase. Nature Physics, 2(1), 48-54. doi:10.1038/nphys199Schwoerer, H., Pfotenhauer, S., Jäckel, O., Amthor, K.-U., Liesfeld, B., Ziegler, W., … Esirkepov, T. (2006). Laser-plasma acceleration of quasi-monoenergetic protons from microstructured targets. Nature, 439(7075), 445-448. doi:10.1038/nature04492Margarone, D., Klimo, O., Kim, I. J., Prokůpek, J., Limpouch, J., Jeong, T. M., … Korn, G. (2012). Laser-Driven Proton Acceleration Enhancement by Nanostructured Foils. Physical Review Letters, 109(23). doi:10.1103/physrevlett.109.234801Flippo, K. A., d’ Humières, E., Gaillard, S. A., Rassuchine, J., Gautier, D. C., Schollmeier, M., … Hegelich, B. M. (2008). Increased efficiency of short-pulse laser-generated proton beams from novel flat-top cone targets. Physics of Plasmas, 15(5), 056709. doi:10.1063/1.291812

Resultados preliminares de la influencia de la temperatura de cultivo sobre la proporción de sexos en el rodaballo (Scophthalmus maximus L.)

Las larvas de tres familias de rodaballos se cultivaron a temperaturas de 15'C, 18'C y 22'C desde el día dos hasta día 90 de vida y a temperatura ambiente hasta el dia 210. En las familias 1 y 2 las proporciones sexuales, determinadas por el fenotipo, oscilaron en los tres grupos entre el 40%- 60%,y no se observaron diferencias siqníñcaffvas entre los diferentes grupos de temperatura (p>0.05). En la familia 3, el porcentaje de hembras fue mayor que el de machos en los tres grupos de temperatura, y además se observó diferencia significativa (p<0.05) entre el grupo de peces cultivados a temperatura fría con respecto a los cultivados en agua ambiente. En tas familias 1 y 2 el sexo genético coincidió en gran medida con~ sexo fenolípico, siendo la discrepancia menor del 10%. Sin embargo, en la familia 3 se observó que el 36,5% de los machos genéticos eran hembras a 15'C, el 29% a 18ºC y el 18% a 23'C. Los resultados sugieren la interacción temperatura-familia en la determinación sexual del rodaballo, que debe ser confirmada en un mayor número de familias.Larvae from three families of turbot were cultured at 15'C, 18'C and 22'C from 2 to 90 days old, and then at ambient temperature until210 daysold. Regarding families 1 and 2, \he sexual proportions determined by \he phenotype varied between 40%·60%, regardless of \he cunure temperature (p>O.05). Gontrary, in family 3, \he percentage of females was higher than for males in all three cunure temperatures. Furthermore, \here were differences (¡¡<O.05) between families cultured at 15'C and 18'C. For families 1 and 2, sex determined by genotype was similarto \hat detennined by the phenotype, wi\h differences <1 0%. Gontrary, for family 3,\he \he percentage of males determined by \he genotype \hat were phenotipycatt¡ females was 36, 29 and 18% for animals cunured at 15'C, 18'C and 22'C, respectively. Results suggest an interaction temperature-family in \he turbot sex determination which should be checked on a higher numberoffamilies

Predictive factors and early biomarkers of response in multiple sclerosis patients treated with natalizumab

There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein–Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach

Bioactive extracts from persimmon waste: influence of extraction conditions and ripeness

In this work, a bioactive persimmon extract was produced from discarded fruits. A central composite design was used to evaluate the effect of different extraction parameters and ripeness stages of persimmon fruits on the total phenolic content and antioxidant activity of the resulting extracts. Significantly greater phenolic contents were obtained from immature persimmon (IP) fruits. The optimum IP extract with the conditions set by the experimental design was industrially up-scaled and its composition and functional properties were evaluated and compared with those obtained under lab-scale conditions. Both extracts contained significant protein (>20%) and phenolic contents (similar to 11-27 mg GA/g dry extract) and displayed significant antiviral activity against murine norovirus and hepatitis A virus. Moreover, the extract showed no toxicity and significantly reduced the fat content and the cellular ageing of Caenorhabditis elegans (C. elegans) without affecting the worm development. These effects were mediated by down-regulation of fat-7, suggesting an anti-lipogenic activity of this extract

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD