DNA Vaccines: Developing New Strategies against Cancer

Due to their rapid and widespread development, DNA vaccines have entered into a variety of human clinical trials for vaccines against various diseases including cancer. Evidence that DNA vaccines are well tolerated and have an excellent safety profile proved to be of advantage as many clinical trials combines the first phase with the second, saving both time and money. It is clear from the results obtained in clinical trials that such DNA vaccines require much improvement in antigen expression and delivery methods to make them sufficiently effective in the clinic. Similarly, it is clear that additional strategies are required to activate effective immunity against poorly immunogenic tumor antigens. Engineering vaccine design for manipulating antigen presentation and processing pathways is one of the most important aspects that can be easily handled in the DNA vaccine technology. Several approaches have been investigated including DNA vaccine engineering, co-delivery of immunomodulatory molecules, safe routes of administration, prime-boost regimen and strategies to break the immunosuppressive networks mechanisms adopted by malignant cells to prevent immune cell function. Combined or single strategies to enhance the efficacy and immunogenicity of DNA vaccines are applied in completed and ongoing clinical trials, where the safety and tolerability of the DNA platform are substantiated. In this review on DNA vaccines, salient aspects on this topic going from basic research to the clinic are evaluated. Some representative DNA cancer vaccine studies are also discussed

Monografías sonoras: el podcast como herramienta educativa en ciencias naturales

La pandemia demostró desafíos en múltiples aspectos de nuestra vida cotidiana y la educación no ha escapado a esta circunstancia. La articulación entre la asignatura Salud Pública y Ambiente con el Proyecto de Extensión Universitaria “Habitar con Salud”, permitió abordar distintas temáticas propuestas desde un anclaje territorial. Dado que son muy relevantes para la coyuntura actual, existe un enorme volumen de material de consulta, siendo un desafío su correcta identificación y clasificación. Las tecnologías digitales actuales abren un amplio abanico de herramientas para usar en el aula y ampliarla más allá de sus paredes, y los podcast son una de ellas. Así, durante el Segundo Cuatrimestre del año 2020, decidimos convertir los trabajos finales en capítulos del Podcast “Una Especie De Ciencia”, trascendiendo el espacio del aula virtual con nuestras lecturas y reflexiones. El conocimiento científico, como actividad social que es, hecho por y para las personas, debe salir del ámbito académico. La comunicación pública de la ciencia permite tomar decisiones con fundamentos hacia el desarrollo de una mejor sociedad. Sobre ello, temáticas tan vigentes como las relacionadas a la salud y el ambiente no pueden esperar ni ser relegadas a un segundo plano: deben ponerse en agenda, y el podcast es una herramienta que permite hacerlo abriendo las fronteras, recreando el conocimiento científico de forma que todos y todas puedan acceder. Así, aprendiendo y, por qué no, jugando, hemos construido de forma colectiva una herramienta que ha logrado extender un puente entre la educación, la evaluación y la comunicación de la ciencia y la tecnología.</p

Monografías sonoras: el podcast como herramienta educativa en ciencias naturales

La pandemia demostró desafíos en múltiples aspectos de nuestra vida cotidiana y la educación no ha escapado a esta circunstancia. La articulación entre la asignatura Salud Pública y Ambiente con el Proyecto de Extensión Universitaria “Habitar con Salud”, permitió abordar distintas temáticas propuestas desde un anclaje territorial. Dado que son muy relevantes para la coyuntura actual, existe un enorme volumen de material de consulta, siendo un desafío su correcta identificación y clasificación. Las tecnologías digitales actuales abren un amplio abanico de herramientas para usar en el aula y ampliarla más allá de sus paredes, y los podcast son una de ellas. Así, durante el Segundo Cuatrimestre del año 2020, decidimos convertir los trabajos finales en capítulos del Podcast “Una Especie De Ciencia”, trascendiendo el espacio del aula virtual con nuestras lecturas y reflexiones. El conocimiento científico, como actividad social que es, hecho por y para las personas, debe salir del ámbito académico. La comunicación pública de la ciencia permite tomar decisiones con fundamentos hacia el desarrollo de una mejor sociedad. Sobre ello, temáticas tan vigentes como las relacionadas a la salud y el ambiente no pueden esperar ni ser relegadas a un segundo plano: deben ponerse en agenda, y el podcast es una herramienta que permite hacerlo abriendo las fronteras, recreando el conocimiento científico de forma que todos y todas puedan acceder. Así, aprendiendo y, por qué no, jugando, hemos construido de forma colectiva una herramienta que ha logrado extender un puente entre la educación, la evaluación y la comunicación de la ciencia y la tecnología

An extra virgin olive oil‐enriched diet improves maternal, placental and cord blood parameters in GDM pregnancies

Aims: To address the effect of a diet enriched in extra virgin olive oil (EVOO) on maternal metabolic parameters and placental proinflammatory markers in Gestational diabetes mellitus (GDM) patients. Methods: Pregnant women at 24-28 weeks of gestation were enrolled: 33 GDM patients which were randomly assigned or not to the EVOO-enriched group and 17 healthy controls. Metabolic parameters were determined. Peroxisome proliferator activated receptor (PPAR) γ and PPARα protein expression, expression of microRNA (miR)-130a and miR-518d (which respectively target these PPAR isoforms) and levels of proinflammatory markers were evaluated in term placentas. Matrix metalloproteinases (MMPs) activity was evaluated in term placentas and umbilical cord blood. Results: GDM patients that received the EVOO-enriched diet showed reduced pregnancy weight gain (GDM-EVOO:10.3 ± 0.9, GDM:14.2 ± 1.4, P =.03) and reduced triglyceridemia (GDM-EVOO:231 ± 14, GDM:292 ± 21, P =.02) compared to the non-EVOO-enriched GDM group. In GDM placentas, the EVOO-enriched diet did not regulate PPARγ protein expression or miR-130a expression, but prevented the reduced PPARα protein expression (P =.02 vs GDM) and the increased miR-518d expression (P =.009 vs GDM). Increased proinflammatory markers (interleukin-1β, tumour necrosis factor-α and nitric oxide overproduction) in GDM placentas were prevented by the EVOO-enriched diet (respectively P =.001, P =.001 and P =.01 vs GDM). MMPs overactivity was prevented in placenta and umbilical cord blood in the EVOO-enriched GDM group (MMP-9: respectively P =.01 and P =.001 vs GDM). Conclusions: A diet enriched in EVOO in GDM patients reduced maternal triglyceridemia and weight gain and has antiinflammatory properties in placenta and umbilical cord blood, possibly mediated by the regulation of PPAR pathways.Fil: Gomez Ribot, Dalmiro Leonardo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Diaz, Esteban. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Fazio, María Victoria. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Gómez, Hebe Lorena. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Fornes, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Macchi, Silvia Beatriz. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Gresta, Carlos Alberto. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Ignacio Pirovano; ArgentinaFil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

A Critical Assessment of Stellar Mass Measurement Methods

In this paper we perform a comprehensive study of the main sources of random and systematic errors in stellar mass measurement for galaxies using their Spectral Energy Distributions (SEDs). We use mock galaxy catalogs with simulated multi-waveband photometry (from U-band to mid-infrared) and known redshift, stellar mass, age and extinction for individual galaxies. Given different parameters affecting stellar mass measurement (photometric S/N ratios, SED fitting errors, systematic effects, the inherent degeneracies and correlated errors), we formulated different simulated galaxy catalogs to quantify these effects individually. We studied the sensitivity of stellar mass estimates to the codes/methods used, population synthesis models, star formation histories, nebular emission line contributions, photometric uncertainties, extinction and age. For each simulated galaxy, the difference between the input stellar masses and those estimated using different simulation catalogs, $\Delta\log(M)$, was calculated and used to identify the most fundamental parameters affecting stellar masses. We measured different components of the error budget, with the results listed as follows: (1). no significant bias was found among different codes/methods, with all having comparable scatter; (2). A source of error is found to be due to photometric uncertainties and low resolution in age and extinction grids; (3). The median of stellar masses among different methods provides a stable measure of the mass associated with any given galaxy; (4). The deviations in stellar mass strongly correlate with those in age, with a weaker correlation with extinction; (5). the scatter in the stellar masses due to free parameters are quantified, with the sensitivity of the stellar mass to both the population synthesis codes and inclusion of nebular emission lines studied.Comment: 33 pages, 20 Figures, Accepted for publication in Astrophysical Journa

CANDELS Multi-wavelength Catalogs: Source Detection and Photometry in the GOODS-South Field

We present a UV-to-mid infrared multi-wavelength catalog in the CANDELS/GOODS-S field, combining the newly obtained CANDELS HST/WFC3 F105W, F125W, and F160W data with existing public data. The catalog is based on source detection in the WFC3 F160W band. The F160W mosaic includes the data from CANDELS deep and wide observations as well as previous ERS and HUDF09 programs. The mosaic reaches a 5$\sigma$ limiting depth (within an aperture of radius 0.17 arcsec) of 27.4, 28.2, and 29.7 AB for CANDELS wide, deep, and HUDF regions, respectively. The catalog contains 34930 sources with the representative 50% completeness reaching 25.9, 26.6, and 28.1 AB in the F160W band for the three regions. In addition to WFC3 bands, the catalog also includes data from UV (U-band from both CTIO/MOSAIC and VLT/VIMOS), optical (HST/ACS F435W, F606W, F775W, F814W, and F850LP), and infrared (HST/WFC3 F098M, VLT/ISAAC Ks, VLT/HAWK-I Ks, and Spitzer/IRAC 3.6, 4.5, 5.8, 8.0 $\mu$m) observations. The catalog is validated via stellar colors, comparison with other published catalogs, zeropoint offsets determined from the best-fit templates of the spectral energy distribution of spectroscopically observed objects, and the accuracy of photometric redshifts. The catalog is able to detect unreddened star-forming (passive) galaxies with stellar mass of 10^{10}M_\odot at a 50% completeness level to z$\sim$3.4 (2.8), 4.6 (3.2), and 7.0 (4.2) in the three regions. As an example of application, the catalog is used to select both star-forming and passive galaxies at z$\sim$2--4 via the Balmer break. It is also used to study the color--magnitude diagram of galaxies at 0<z<4.Comment: The full resolution article is now published in ApJS (2013, 207, 24). 22 pages, 21 figures, and 5 tables. The catalogue is available on the CANDELS website: http://candels.ucolick.org/data_access/GOODS-S.html MAST: http://archive.stsci.edu/prepds/candels and Rainbow Database: https://arcoiris.ucolick.org/Rainbow_navigator_public and https://rainbowx.fis.ucm.es/Rainbow_navigator_publi

Epigenetic Immune Remodeling of Mesothelioma Cells: A New Strategy to Improve the Efficacy of Immunotherapy

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a severe progno- sis, and with a long-standing need for more effective therapeutic approaches. However, treatment with immune checkpoint inhibitors is becoming an increasingly effective strategy for MPM pa- tients. In this scenario, epigenetic modifications may negatively regulate the interplay between immune and malignant cells within the tumor microenvironment, thus contributing to the highly immunosuppressive contexture of MPM that may limit the efficacy of immunotherapy. Aiming to further improve prospectively the clinical efficacy of immunotherapeutic approaches in MPM, we investigated the immunomodulatory potential of different classes of epigenetic drugs (i.e., DNA hypomethylating agent (DHA) guadecitabine, histone deacetylase inhibitors VPA and SAHA, or EZH2 inhibitors EPZ-6438) in epithelioid, biphasic, and sarcomatoid MPM cell lines, by cytofluo- rimetric and real-time PCR analyses. We also characterized the effects of the DHA, guadecitabine, on the gene expression profiles (GEP) of the investigated MPM cell lines by the nCounter platform. Among investigated drugs, exposure of MPM cells to guadecitabine, either alone or in combination with VPA, SAHA and EPZ-6438 demonstrated to be the main driver of the induction/upregulation of immune molecules functionally crucial in host-tumor interaction (i.e., HLA class I, ICAM-1 and cancer testis antigens) in all three MPM subtypes investigated. Additionally, GEP demonstrated that treatment with guadecitabine led to the activation of genes involved in several immune-related func- tional classes mainly in the sarcomatoid subtype. Furthermore, among investigated MPM subtypes, DHA-induced CDH1 expression that contributes to restoring the epithelial phenotype was highest in sarcomatoid cells. Altogether, our results contribute to providing the rationale to develop new epigenetically-based immunotherapeutic approaches for MPM patients, potentially tailored to the specific histologic subtypes

The CANDELS/SHARDS multiwavelength catalog in GOODS-N : photometry, photometric redshifts, stellar masses, emission-line fluxes, and star formation rates

We present a WFC3 F160W (H-band) selected catalog in the CANDELS/GOODS-N field containing photometry from the ultraviolet (UV) to the far-infrared (IR), photometric redshifts, and stellar parameters derived from the analysis of the multiwavelength data. The catalog contains 35,445 sources over the 171 arcmin(2) of the CANDELS F160W mosaic. The 5 sigma detection limits (within an aperture of radius 0 ''.17) of the mosaic range between H = 27.8, 28.2, and 28.7 in the wide, intermediate, and deep regions, which span approximately 50%, 15%, and 35% of the total area. The multiwavelength photometry includes broadband data from the UV (U band from KPNO and LBC), optical (HST/ACS F435W, F606W, F775W, F814W, and F850LP), near-to-mid IR (HST/WFC3 F105W, F125W, F140W, and F160W; Subaru/MOIRCS Ks; CFHT/Megacam K; and Spitzer/IRAC 3.6, 4.5, 5.8, and 8.0 mu m), and far-IR (Spitzer/MIPS 24 mu m, HERSCHEL/PACS 100 and 160 mu m, SPIRE 250, 350 and 500 mu m) observations. In addition, the catalog also includes optical medium-band data (R similar to 50) in 25 consecutive bands, lambda = 500-950 nm, from the SHARDS survey and WFC3 IR spectroscopic observations with the G102 and G141 grisms (R similar to 210 and 130). The use of higher spectral resolution data to estimate photometric redshifts provides very high, and nearly uniform, precision from z = 0-2.5. The comparison to 1485 good-quality spectroscopic redshifts up to z similar to 3 yields Delta z/(1 + z(spec)) = 0.0032 and an outlier fraction of eta = 4.3%. In addition to the multiband photometry, we release value-added catalogs with emission-line fluxes, stellar masses, dust attenuations, UV- and IR-based star formation rates, and rest-frame colors

Selective fatty acid amide hydrolase inhibitors as potential novel antiepileptic agents

Temporal lobe epilepsy is the most common form of epilepsy, and current antiepileptic drugs are ineffective in many patients. The endocannabinoid system has been associated with an on-demand protective response to seizures. Blocking endocannabinoid catabolism would elicit antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation of the hippocampal maximal dentate activation. Notably, 2a did not affect hippocampal dentate gyrus long-term synaptic plasticity. These data prompted our further endeavor aiming at discovering new antiepileptic agents, developing a new set of FAAH inhibitors (3a–m). Biological studies highlighted 3h and 3m as the best performing analogues to be further investigated. In cell-based studies, using a neuroblastoma cell line, 3h and 3m could reduce the oxinflammation state by decreasing DNA-binding activity of NF-kB p65, devoid of cytotoxic effect. Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a

CANDELS multi-wavelength catalogs: source identification and photometry in the CANDELS Extended Groth Strip

We present a 0.4-8?m multi-wavelength photometric catalog in the Extended Groth Strip (EGS) field. This catalog is built on the Hubble Space Telescope (HST) WFC3 and ACS data from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS), and it incorporates the existing HST data from the All-wavelength Extended Groth strip International Survey (AEGIS) and the 3D-HST program. The catalog is based on detections in the F160W band reaching a depth of F160W=26.62 AB (90% completeness, point-sources). It includes the photometry for 41457 objects over an area of ~ 206 arcmin2 in the following bands: HST ACS F606W and F814W; HST WFC3 F125W, F140W and F160W; CFHT/Megacam u?, g?, r?, i? and z?; CFHT/WIRCAM J, H and KS; Mayall/NEWFIRM J1, J2, J3, H1, H2, K; Spitzer IRAC 3.6?m, 4.5?m, 5.8?m and 8.0?m. We are also releasing value-added catalogs that provide robust photometric redshifts and stellar mass measurements. The catalogs are publicly available through the CANDELS repository