Influence of 1 and 25 Hz,1.5 mT Magnetic Fields on Antitumor Drug Potency in a Human Adenocarcinoma Cell Line

The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1 cch . The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P < 0.01), exhibiting 6.1% of survival at 47.5 mg/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 mg/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P < 0.001). Cisplatin showed a significant reduction in the % of survival (44.2-39.1%, P < 0.05) at 25 Hz and 47.5 mg/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1 cch , with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation

Excitation power dependence of the Purcell effect in photonic crystalmicrocavity lasers with quantum wires

[EN] The Purcell effect dependence on the excitation power is studied in photonic crystal microcavity lasers embedding InAs/InP quantum wires. In the case of non-lasing modes, the Purcell effect has low dependence on the optical pumping, attributable to an exciton dynamics combining free and localized excitons. In the case of lasing modes, the influence of the stimulated emission makes ambiguous the determination of the Purcell factor. We have found that this ambiguity can be avoided by measuring the dependence of the decay time on the excitation power. These results provide insights in the determination of the Purcell factor in microcavity lasers.We want to acknowledge financial support from the Spanish MICINN through grants (Nos. S-0505-TIC-0191, TEC2008-06756-C03-01/-03, TEC2011-29045-C04-03, TEC2011-29120-C05-01/04, and CAM S2009ESP-1503). J.C.-F. thanks the Spanish MCI for his FPI grant (No. BES-2006-12300).Canet-Ferrer, J.; Prieto, I.; Muñoz Matutano, G.; Martínez, L.; Muñoz-Camuniez, L.; Llorens, J.; Fuster, D.... (2013). Excitation power dependence of the Purcell effect in photonic crystalmicrocavity lasers with quantum wires. Applied Physics Letters. 102(20). https://doi.org/10.1063/1.4807439S10220Gérard, J., Sermage, B., Gayral, B., Legrand, B., Costard, E., & Thierry-Mieg, V. (1998). Enhanced Spontaneous Emission by Quantum Boxes in a Monolithic Optical Microcavity. Physical Review Letters, 81(5), 1110-1113. doi:10.1103/physrevlett.81.1110Englund, D., Fattal, D., Waks, E., Solomon, G., Zhang, B., Nakaoka, T., … Vučković, J. (2005). Controlling the Spontaneous Emission Rate of Single Quantum Dots in a Two-Dimensional Photonic Crystal. Physical Review Letters, 95(1). doi:10.1103/physrevlett.95.013904Munsch, M., Mosset, A., Auffèves, A., Seidelin, S., Poizat, J. P., Gérard, J.-M., … Senellart, P. (2009). Continuous-wave versus time-resolved measurements of Purcell factors for quantum dots in semiconductor microcavities. Physical Review B, 80(11). doi:10.1103/physrevb.80.115312Yoshie, T., Scherer, A., Hendrickson, J., Khitrova, G., Gibbs, H. M., Rupper, G., … Deppe, D. G. (2004). Vacuum Rabi splitting with a single quantum dot in a photonic crystal nanocavity. Nature, 432(7014), 200-203. doi:10.1038/nature03119Badolato, A. (2005). Deterministic Coupling of Single Quantum Dots to Single Nanocavity Modes. Science, 308(5725), 1158-1161. doi:10.1126/science.1109815Hennessy, K., Badolato, A., Winger, M., Gerace, D., Atatüre, M., Gulde, S., … Imamoğlu, A. (2007). Quantum nature of a strongly coupled single quantum dot–cavity system. Nature, 445(7130), 896-899. doi:10.1038/nature05586Strauf, S. (2010). Towards efficient quantum sources. Nature Photonics, 4(3), 132-134. doi:10.1038/nphoton.2010.11Altug, H., Englund, D., & Vučković, J. (2006). Ultrafast photonic crystal nanocavity laser. Nature Physics, 2(7), 484-488. doi:10.1038/nphys343Azzini, S., Gerace, D., Galli, M., Sagnes, I., Braive, R., Lemaître, A., … Bajoni, D. (2011). Ultra-low threshold polariton lasing in photonic crystal cavities. Applied Physics Letters, 99(11), 111106. doi:10.1063/1.3638469Nozaki, K., Kita, S., & Baba, T. (2007). Room temperature continuous wave operation and controlled spontaneous emission in ultrasmall photonic crystal nanolaser. Optics Express, 15(12), 7506. doi:10.1364/oe.15.007506Strauf, S., Hennessy, K., Rakher, M. T., Choi, Y.-S., Badolato, A., Andreani, L. C., … Bouwmeester, D. (2006). Self-Tuned Quantum Dot Gain in Photonic Crystal Lasers. Physical Review Letters, 96(12). doi:10.1103/physrevlett.96.127404Kippenberg, T. J., Spillane, S. M., & Vahala, K. J. (2004). Demonstration of ultra-high-Q small mode volume toroid microcavities on a chip. Applied Physics Letters, 85(25), 6113-6115. doi:10.1063/1.1833556Arakawa, Y., & Sakaki, H. (1982). Multidimensional quantum well laser and temperature dependence of its threshold current. Applied Physics Letters, 40(11), 939-941. doi:10.1063/1.92959Kapon, E. (1992). Quantum wire lasers. Proceedings of the IEEE, 80(3), 398-410. doi:10.1109/5.135356Canet-Ferrer, J., Munoz-Matutano, G., Fuster, D., Alen, B., Gonzalez, Y., Gonzalez, L., & Martinez-Pastor, J. P. (2011). Localization effects on recombination dynamics in InAs/InP self-assembled quantum wires emitting at 1.5 μm. Journal of Applied Physics, 110(10), 103502. doi:10.1063/1.3660260Alén, B., Martı́nez-Pastor, J., Garcı́a-Cristobal, A., González, L., & Garcı́a, J. M. (2001). Optical transitions and excitonic recombination in InAs/InP self-assembled quantum wires. Applied Physics Letters, 78(25), 4025-4027. doi:10.1063/1.1379991Cao, M., Daste, P., Miyamoto, Y., Miyake, Y., Nogiwa, S., Arai, S., … Suematsu, Y. (1988). GaInAsP/InP single-quantum-well (SQW) laser with wire-like active region towards quantum wire laser. Electronics Letters, 24(13), 824. doi:10.1049/el:19880561Atlasov, K. A., Calic, M., Karlsson, K. F., Gallo, P., Rudra, A., Dwir, B., & Kapon, E. (2009). Photonic-crystal microcavity laser with site-controlled quantum-wire active medium. Optics Express, 17(20), 18178. doi:10.1364/oe.17.018178Martinez, L. J., Alén, B., Prieto, I., Fuster, D., González, L., González, Y., … Postigo, P. A. (2009). Room temperature continuous wave operation in a photonic crystal microcavity laser with a single layer of InAs/InP self-assembled quantum wires. Optics Express, 17(17), 14993. doi:10.1364/oe.17.014993Mao, M.-H., & Chien, H.-C. (2012). Transient behaviors of current-injection quantum-dot microdisk lasers. Optics Express, 20(3), 3302. doi:10.1364/oe.20.003302Gregersen, N., Suhr, T., Lorke, M., & Mørk, J. (2012). Quantum-dot nano-cavity lasers with Purcell-enhanced stimulated emission. 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Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency through inhibition of CDK8/19 Mediator kinases

Pluripotent stem cells (PSCs) transition between cell states in vitro and reflect developmental changes in the early embryo. PSCs can be stabilized in the naïve state by blocking extracellular differentiation stimuli, particularly FGF-MEK signaling. Here, we report that multiple features of the naïve state in human and mouse PSCs can be recapitulated without affecting FGF-MEK-signaling or global DNA methylation. Mechanistically, chemical inhibition of CDK8 and CDK19 kinases removes their ability to repress the Mediator complex at enhancers. Thus CDK8/19 inhibition increases Mediator-driven recruitment of RNA Pol II to promoters and enhancers. This efficiently stabilizes the naïve transcriptional program and confers resistance to enhancer perturbation by BRD4 inhibition. Moreover, naïve pluripotency during embryonic development coincides with a reduction in CDK8/19. We conclude that global hyperactivation of enhancers drives naïve pluripotency, and this can be achieved in vitro by inhibiting CDK8/19 kinase activity. These principles may apply to other contexts of cellular plasticity

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease

Background: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Methods: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Results: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). Conclusions: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD

Transcriptome dynamics of a broad host-range cyanophage and its hosts

Cyanobacteria are highly abundant in the oceans and are constantly exposed to lytic viruses. The T4-like cyanomyoviruses are abundant in the marine environment and have broad host-ranges relative to other cyanophages. It is currently unknown whether broad host-range phages specifically tailor their infection program for each host, or employ the same program irrespective of the host infected. Also unknown is how different hosts respond to infection by the same phage. Here we used microarray and RNA-seq analyses to investigate the interaction between the Syn9 T4-like cyanophage and three phylogenetically, ecologically and genomically distinct marine Synechococcus strains: WH7803, WH8102 and WH8109. Strikingly, Syn9 led a nearly identical infection and transcriptional program in all three hosts. Different to previous assumptions for T4-like cyanophages, three temporally regulated gene expression classes were observed. Furthermore, a novel regulatory element controlled early-gene transcription, and host-like promoters drove middle gene transcription, different to the regulatory paradigm for T4. Similar results were found for the P-TIM40 phage during infection of Prochlorococcus NATL2A. Moreover, genomic and metagenomic analyses indicate that these regulatory elements are abundant and conserved among T4-like cyanophages. In contrast to the near-identical transcriptional program employed by Syn9, host responses to infection involved host-specific genes primarily located in hypervariable genomic islands, substantiating islands as a major axis of phage-cyanobacteria interactions. Our findings suggest that the ability of broad host-range phages to infect multiple hosts is more likely dependent on the effectiveness of host defense strategies than on differential tailoring of the infection process by the phage

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

Listado de especies y subespecies cavernícolas (hipogeas) consideradas como troglobias y estigobias de la península ibérica e islas Baleares

La fauna hipogea o cavernícola ibero-balear ha sido a lo largo de muchos años puesta en evidencia por numerosos zoólogos en las distintas disciplinas. Especialistas de los distintos grupos faunísticos capaces de colonizar las cuevas y las aguas subterráneas que las recorren. Hoy sabemos que esta diversidad de troglobios y estigobios alcanza un total de 1364 taxones: 1285 especies y 79 subespecies hipogeas (cavernícolas) pertenecientes a cuatro filos: Plathyhelminthes (2), Annelida (23), Mollusca (122) y Arthropoda (1217) en todo el territorio ibero-balear. Una fauna que cuenta con numerosos ejemplos de elementos relictos de especial interés paleogeográfico. De la totalidad de taxones hipogeos o cavernícolas del territorio ibero balear, 438 taxones (430 especies y 8 subespecies) son estigobios y 926 taxones (852 especies y 74 subespecies) son troglobios. En lo referente a la distribución de los taxones troglobios es el distrito Cantábrico el que posee una mayor riqueza en especies y subespecies, un total de 208, seguido del Vasco con 163 taxones, el Pirenaico con 153 y el Bético con 142. Algo menos diversos son los distritos Levantino (124 taxones) y Catalán (104 taxones), seguidos de lejos por el Lusitánico con 46 taxones, el Balear con 41 y el Central con tan sólo 19. Entre los estigobios 156 especies y subespecies pueblan las aguas subterráneas de las regiones delimitadas por las cuecas lusitánicas. Le siguen en diversidad las cuencas pirenaicas con 154 taxones estigobios, las béticas con 114 y por último las aguas del subsuelo de las cuencas baleáricas con 47 taxones estigobios, algunos de los cuales son talaso-estigobios, propios de las aguas marinas costeras

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)