AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells. Interference with the Akt/NF-kB survival pathway

8 páginas, 5 figuras -- PAGS nros. 572-579Clinical treatment of B-cell chronic lymphocytic leukemia (B-CLL) is limited by the progressive drug resistance and nonselectivity of most drugs towards malignant cells. Depsipeptides are present in certain bacteria and display potent antitumor activity. We have studied the effect of the novel cyclodepsipeptide AT514 (serratamolide) from Serratia marcescens on B-CLL cell viability. AT514 induced apoptosis of B-CLL cells from the 21 patients studied, as confirmed by Annexin-V binding and nuclei condensation, with an average IC50 of 13 M. AT514 was effective in those B-CLL cases resistant to fludarabine, but had no effect on normal PBL. AT514 preferentially activated the intrinsic apoptotic pathway, as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9 and -3, but not of caspase-8. Importantly, AT514 interfered with phosphatidylinositol-3 kinase and protein kinase C survival signals since it increased the apoptotic effect of LY294002 and BisI inhibitors, and induced Akt dephosphorylation at Ser 473. AT514 also decreased NF-B activity by dramatically reducing the levels of p65 in B-CLL. This was confirmed on functional assays using NF-B-luc-transfected Raji cells and transgenic mice. Our results establish that AT514 induces apoptosis of primary B-CLL cells and could be useful for clinical treatment of this malignancyThis work was supported by grants 08.3/0030.1/2003 from the Comunidad Autónoma de Madrid, SAF2003-00824 from the Ministerio de Ciencia y Tecnología (MCyT), and 01/1183 from Fondo de Investigación Sanitaria (to AGP); and CIDEM Grant 301888 (Generalitat de Catalunya)/Fundació Bosch i Gimpera, to RPT). E Escobar and E López-Martín were supported by fellowships from MCyTPeer reviewe

Generalized Casimir forces in non-equilibrium systems

In the present work we propose a method to determine fluctuation induced forces in non equilibrium systems. These forces are the analogue of the well known Casimir forces, which were originally introduced in Quantum Field theory and later extended to the area of Critical Phenomena. The procedure starts from the observation that many non equilibrium systems exhibit long-range correlations and the associated structure factors diverge in the long wavelength limit. The introduction of external bodies into such systems in general modifies the spectrum of these fluctuations and leads to the appearance of a net force between these bodies. The mechanism is illustrated by means of a simple example: a reaction diffusion equation with random noises.Comment: Submitted to Europhysics Letters. 7 pages, 2 figure

Reliability of a handball specific strength test battery and the association with sprint and throwing performance in young handball players

[EN] BACKGROUND: A greater motivation for coaches to be more involved in assessment could be the development of specific strength tests closer to specific handball tasks. Therefore, the aims were to determine the reliability of a handball specific strength test battery in young handball players using a functional electromechanical dynamometer (FEMD) and to evaluate the association between the strength test battery and performance measurements. METHODS: Thirty-two young handball players (25% males and 75% females) performed a repeated-measurement design over four weeks. The players conducted one session per week, with each measurement consisting of two isometric tests to obtain isometric peak force, and four incremental tests. Moreover, performance handball tests (sprint and throwing velocity [TV]) were recorded. RESULTS: The reliability of the whole handball specific strength tests was very high for the peak and mean strength (ICC=0.70-0.85; CV=8.49- 13.99; SEM=0.44-0.67 kg). The step forward had a moderate association with 5 to 10 meters’ time. The highest correlation between TVmean was found with the peak strength of standing lift and between TVpeak with peak strength of unilateral throw. The sprint total time could be explained by Body Mass Index and peak strength of the standing lift in the 40% and the TVpeak could be explained by arm span and mean strength of the standing lift in the 68%. CONCLUSIONS: The high reliability for all exercises and the significant correlation with handball performance (sprint time and TV) allow us to include these tests in handball team evaluation and training.S

Dynamical approach to the Casimir effect

Casimir forces can appear between intrusions placed in different media driven by several fluctuation mechanisms, either in equilibrium or out of it. Herein, we develop a general formalism to obtain such forces from the dynamical equations of the fluctuating medium, the statistical properties of the driving noise, and the boundary conditions of the intrusions (which simulate the interaction between the intrusions and the medium). As a result, an explicit formula for the Casimir force over the intrusions is derived. This formalism contains the thermal Casimir effect as a particular limit and generalizes the study of the Casimir effect to such systems through their dynamical equations, with no appeal to their Hamiltonian, if any exists. In particular, we study the Casimir force between two infinite parallel plates with Dirichlet or Neumann boundary conditions, immersed in several media with finite correlation lengths (reaction--diffusion system, liquid crystals, and two coupled fields with non-Hermitian evolution equations). The driving Gaussian noises have vanishing or finite spatial or temporal correlation lengths; in the first case, equilibrium is reobtained and finite correlations produce nonequilibrium dynamics. The results obtained show that, generally, nonequilibrium dynamics leads to Casimir forces, whereas Casimir forces are obtained in equilibrium dynamics if the stress tensor is anisotropic.Comment: 12 pages, 1 figur

Proyecto LIFE Ammonia Trapping: planta piloto para la captura de amoniaco del purín

Las emisiones de amoniaco son uno de los contaminantes más importantes generados en las actividades agrícolas y ganaderas, estos sectores son los responsables de más del 93% de las emisiones de amoniaco en la UE. Dichas emisiones causan problemas medioambientales y de salud, por lo que la Unión Europea trata de reducirlas desde el año 2010 con la Directiva NEC 2001/81/CE sobre techos de emisiones, la cual ha sido revisada a través de la Directiva 2016/2284/EU. El proyecto Life Ammonia Trapping tiene como principal objetivo reducir las emisiones de amoniaco de granjas porcinas y avícolas, a través de la aplicación de una nueva tecnología de membranas permeables a los gases. En este trabajo se presentan resultados del primer estudio a escala piloto con la tecnología de membranas permeables a los gases, llevado a cabo en una granja porcina. De acuerdo con estos datos se ha conseguido una recuperación de amoníaco del 66,2% en el prototipo estudiado

Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance

Background: Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months. Methods: Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA =10 ng/mL, cT1c-T2a, Grade group 1, =2 cores, and =5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group =2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher’s exact test, as appropriate established differences between groups of reclassification. Results: A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume. Conclusions: Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management

Genotype and phenotype correlations in diabetic patients in Uruguay

ABSTRACT. To differentiate among different types of diabetes is becom-ing an increasingly challenging task. We investigated whether the patient’s genetic profile is useful to identify the particular type of diabetes, to deter-mine the corresponding hyperglycemia pathogenesis and treat accordingly. Three hundred and thirty-eight diabetic patients, diagnosed according to American Diabetes Association criteria, were recruited from 2004 to 2008 in diabetes health reference centers. We analyzed the major gene for type 1 diabetes susceptibility (HLA DQ/DR). In order to improve our understand-ing of the pathogenesis of the resulting hyperglycemia and to implement a more adequate treatment for the patients, we reclassified our sample ac-1353 ©FUNPEC-RP www.funpecrp.com.brGenetics and Molecular Research 8 (4): 1352-1358 (2009) Genotype and phenotype correlations in diabetic patients cording to the presence or absence of the genetic markers. We found that a higher percentage of people than expected have immunological disease, in

Stellar populations of galaxies in the ALHAMBRA survey up to z∼1z \sim 1. I. MUFFIT: A Multi-Filter Fitting code for stellar population diagnostics

We present MUFFIT, a new generic code optimized to retrieve the main stellar population parameters of galaxies in photometric multi-filter surveys, and we check its reliability and feasibility with real galaxy data from the ALHAMBRA survey. Making use of an error-weighted $\chi^2$-test, we compare the multi-filter fluxes of galaxies with the synthetic photometry of mixtures of two single stellar populations at different redshifts and extinctions, to provide through a Monte Carlo method the most likely range of stellar population parameters (mainly ages and metallicities), extinctions, redshifts, and stellar masses. To improve the diagnostic reliability, MUFFIT identifies and removes from the analysis those bands that are significantly affected by emission lines. We highlight that the retrieved age-metallicity locus for a sample of $z \le 0.22$ early-type galaxies in ALHAMBRA at different stellar mass bins are in very good agreement with the ones from SDSS spectroscopic diagnostics. Moreover, a one-to-one comparison between the redshifts, ages, metallicities, and stellar masses derived spectroscopically for SDSS and by MUFFIT for ALHAMBRA reveals good qualitative agreements in all the parameters. In addition, and using as input the results from photometric-redshift codes, MUFFIT improves the photometric-redshift accuracy by $\sim 10$-$20\%$, and it also detects nebular emissions in galaxies, providing physical information about their strengths. Our results show the potential of multi-filter galaxy data to conduct reliable stellar population studies with the appropiate analysis techniques, as MUFFIT.Comment: 31 pages, 18 figures, accepted for publication in A&