PHANGS–JWST First Results: Dust-embedded Star Clusters in NGC 7496 Selected via 3.3μm PAH Emission

The earliest stages of star formation occur enshrouded in dust and are not observable in the optical. Here we leverage the extraordinary new high-resolution infrared imaging from JWST to begin the study of dust-embedded star clusters in nearby galaxies throughout the Local Volume. We present a technique for identifying dustembedded clusters in NGC 7496 (18.7 Mpc), the first galaxy to be observed by the PHANGS–JWST Cycle 1 Treasury Survey. We select sources that have strong 3.3 μm PAH emission based on a F300M − F335M color excess and identify 67 candidate embedded clusters. Only eight of these are found in the PHANGS-HST optically selected cluster catalog, and all are young (six have SED fit ages of ∼1 Myr). We find that this sample of embedded cluster candidates may significantly increase the census of young clusters in NGC 7496 from the PHANGS-HST catalog; the number of clusters younger than ∼2 Myr could be increased by a factor of 2. Candidates are preferentially located in dust lanes and are coincident with the peaks in the PHANGS-ALMA CO (2–1) maps. We take a first look at concentration indices, luminosity functions, SEDs spanning from 2700 Å to 21 μm, and stellar masses (estimated to be between ∼10⁴ and 10⁵ M☉). The methods tested here provide a basis for future work to derive accurate constraints on the physical properties of embedded clusters, characterize the completeness of cluster samples, and expand analysis to all 19 galaxies in the PHANGS–JWST sample, which will enable basic unsolved problems in star formation and cluster evolution to be addressed.La lista completa de autores que integran el documento puede consultarse en el archivo.Instituto de Astrofísica de La Plat

PHANGS–JWST First Results: Massive Young Star Clusters and New Insights from JWST Observations of NGC1365

A primary new capability of JWST is the ability to penetrate the dust in star-forming galaxies to identify and study the properties of young star clusters that remain embedded in dust and gas. In this Letter we combine new infrared images taken with JWST with our optical Hubble Space Telescope (HST) images of the starbursting barred (Seyfert2) spiral galaxy NGC 1365. We find that this galaxy has the richest population of massive young clusters of any known galaxy within 30 Mpc, with ∼30 star clusters that are more massive than 106Me and younger than 10 Myr. Sixteen of these clusters are newly discovered from our JWST observations. An examination of the optical images reveals that 4 of 30 (∼13%) are so deeply embedded that they cannot be seen in the Hubble I band (AV 10 mag), and that 11 of 30 (∼37%) are missing in the HST B band, so age and mass estimates from optical measurements alone are challenging. These numbers suggest that massive clusters in NGC 1365 remain completely obscured in the visible for ∼1.3 ± 0.7 Myr and are either completely or partially obscured for ∼3.7 ± 1.1 Myr. We also use the JWST observations to gain new insights into the triggering of star cluster formation by the collision of gas and dust streamers with gas and dust in the bar. The JWST images reveal previously unknown structures (e.g., bridges and overshoot regions from stars that form in the bar) that help us better understand the orbital dynamics of barred galaxies and associated star-forming rings. Finally, we note that the excellent spatial resolution of the NIRCAM F200W filter provides a better way to separate barely resolved compact clusters from individual stars based on their sizes.La lista completa de autores que integran el documento puede consultarse en el archivo.Instituto de Astrofísica de La Plat

The PHANGS–JWST Treasury Survey: Star Formation, Feedback, and Dust Physics at High Angular Resolution in Nearby GalaxieS

The PHANGS collaboration has been building a reference data set for the multiscale, multiphase study of star formation and the interstellar medium (ISM) in nearby galaxies. With the successful launch and commissioning of JWST, we can now obtain high-resolution infrared imaging to probe the youngest stellar populations and dust emission on the scales of star clusters and molecular clouds (∼5–50 pc). In Cycle 1, PHANGS is conducting an eight-band imaging survey from 2 to 21 μm of 19 nearby spiral galaxies. Optical integral field spectroscopy, CO(2–1) mapping, and UV-optical imaging for all 19 galaxies have been obtained through large programs with ALMA, VLT-MUSE, and Hubble. PHANGS–JWST enables a full inventory of star formation, accurate measurement of the mass and age of star clusters, identification of the youngest embedded stellar populations, and characterization of the physical state of small dust grains. When combined with Hubble catalogs of ∼10,000 star clusters, MUSE spectroscopic mapping of ∼20,000 H II regions, and ∼12,000 ALMA-identified molecular clouds, it becomes possible to measure the timescales and efficiencies of the earliest phases of star formation and feedback, build an empirical model of the dependence of small dust grain properties on local ISM conditions, and test our understanding of how dust-reprocessed starlight traces star formation activity, all across a diversity of galactic environments. Here we describe the PHANGS–JWST Treasury survey, present the remarkable imaging obtained in the first few months of science operations, and provide context for the initial results presented in the first series of PHANGS–JWST publications.La lista completa de autores que integran el documento puede consultarse en el archivo.Instituto de Astrofísica de La Plat

Study of the mechanisms of resistance to tamoxifen and palbociclib in breast cancer

El cáncer de mama es la neoplasia maligna con la incidencia y mortalidad más alta en mujeres en el mundo. Aproximadamente el 70% de los tumores de mama expresan receptores de estrógenos (ER) y de progesterona (PR) y son por eso susceptibles al tratamiento con inhibidores hormonales como el tamoxifeno. Si bien la terapia hormonal es eficaz para el tratamiento de estos tumores, un alto porcentaje de los pacientes eventualmente recae a esta terapia. Recientemente se ha aprobado el uso de inhibidores de ciclo celular, como el palbociclib, para el tratamiento de los pacientes que recaen a la terapia endócrina o que presentan cáncer de mama metastásico. Sin embargo, de igual forma que con el tratamiento hormonal, estos pacientes eventualmente dejan de responder al tratamiento o incluso algunos no responden desde el comienzo. El objetivo general de este trabajo fue estudiar los mecanismos de resistencia asociados al tratamiento con tamoxifeno y con palbociclib, para poder proponer mejores estrategias terapéuticas para los pacientes que recaen a los mismos, así como también para evitar o retrasar el desarrollo de resistencia. Para esto, utilizamos las líneas de cáncer de mama humano T47D y MCF-7 para generar variantes resistentes a ambas drogas por presión selectiva con dichos agentes por 12 a 24 meses. Generamos primero las variantes resistentes a tamoxifeno (T47D-TR y MCF-7-TR) y a palbociclib (T47D-PR y MCF-7-PR), y luego a partir de las resistentes a tamoxifeno generamos las variantes doble resistentes a tamoxifeno y palbociclib (T47D-TPR y MCF-7-TPR), simulando la secuencia terapéutica utilizada en la clínica. Evaluamos la morfología de las líneas resistentes creciendo en 2D y observamos que presentan mayor atipia celular que las líneas parentales, forman estructuras irregulares y desorganizadas creciendo en 3D sobre Geltrex y en suspensión como mamosferas, lo cual se correlaciona con una expresión aberrante o reducida de E-cadherina. Además, encontramos que la variante resistente a tamoxifeno T47D-TR presenta un aumento en la capacidad de formar mamosferas, así como en la expresión de marcadores de stemness. A su vez, tanto la variante resistente a tamoxifeno MCF-7-TR como la resistente a palbociclib MCF-7-PR presentan una mayor capacidad migratoria que la línea wild type. Por otra parte, las variantes resistentes presentan una menor tasa de proliferación que la línea parental, tanto in vitro como in vivo. En contraposición a esto, encontramos aumento en la expresión de proteínas del ciclo celular como ciclina D1, ciclina E2, CDK4, CDK6 y CDK1 y disminución en Rb, dependiendo de la variante analizada. Encontramos también una menor expresión de ER y PR en las variantes resistentes, así como también un aumento en la activación de la vía de PI3K/AKT/mTOR a nivel de AKT o de la proteína ribosomal S6, y un aumento en PKCα. Evaluamos la sensibilidad in vitro de las variantes a inhibidores de PI3K/AKT/mTOR que actúan a distintos niveles de la vía, y encontramos un mayor efecto inhibitorio utilizando rapamicina (inhibidor de mTOR) que utilizando alpelisib (inhibidor de PI3Kα). Además, observamos que la combinación de rapamicina con palbociclib es más efectiva que los tratamientos, tanto in vitro como in vivo, no solo en reducir la proliferación y el crecimiento tumoral, sino también inhibiendo la expresión de proteínas del ciclo celular y la activación de la vía de PI3K/AKT/mTOR. Finalmente, para validar los resultados obtenidos en las líneas celulares, utilizamos xenotrasplantes derivados de pacientes (PDX) obtenidos a partir de biopsias de pacientes con tumores de mama ER+, sensibles y resistentes a tamoxifeno y palbociclib. Disgregamos los PDXs para obtener células individuales, las cuales fueron crecidas ex-vivo en 3D sobre Matrigel. Observamos que la mayoría de los cultivos son sensibles al tratamiento con alpelisib (inhibidor de PI3Kα). Por otra parte, la totalidad de los PDXs analizados son sensibles al tratamiento con everolimus (inhibidor de mTOR), independientemente de la presencia de mutaciones o alteraciones en genes de la vía de PI3K/AKT/mTOR. Además, la triple combinación de palbociclib con everolimus y fulvestrant (inhibidor de ER) es más efectiva que las drogas individuales, no solo inhibiendo proteínas del ciclo celular sino también la activación de la vía de PI3K/AKT/mTOR. En conjunto, nuestros resultados indican que el tratamiento combinado de palbociclib con inhibidores de mTOR es efectivo tanto en un contexto de resistencia a tamoxifeno como a palbociclib, inhibiendo en paralelo tanto la proliferación celular y el crecimiento tumoral como la activación del eje ciclina D1/CDK4/6/Rb y de la vía de PI3K/AKT/mTOR. Esta combinación podría evitar una reactivación de esta vía downstream mTOR y así retrasar el desarrollo de resistencia. En conclusión, en este trabajo generamos y caracterizamos modelos experimentales de resistencia adquirida a tamoxifeno y a palbociclib, simulando la secuencia terapéutica utilizada en la clínica. Estos modelos son útiles para estudiar tanto en cultivo celular como in vivo los mecanismos asociados al desarrollo de resistencia, para de esta manera poder proponer mejores estrategias terapéuticas para el tratamiento de los tumores de mama que recaen a estos esquemas, así como también contribuir a la identificación de posibles biomarcadores de respuesta terapéutica.Breast cancer is the malignant neoplasm with the highest incidence and mortality in women worldwide. Approximately 70% of breast tumors express estrogen (ER) and progesterone (PR) receptors and are therefore sensitive to endocrine inhibitors, such as tamoxifen. Although endocrine therapy is effective for the treatment of these tumors, a significant amount of patients eventually relapse. Recently, the use of cell cycle inhibitors such as palbociclib has been approved for the treatment of patients that relapse to hormone therapy or have metastatic breast cancer. However, patients ultimately relapse to this treatment, or do not respond from the beginning. The aim of this work was to study the mechanisms of resistance associated with tamoxifen and palbociclib treatment, in order to propose better therapeutic strategies for patients to avoid or delay cancer relapse. To accomplish this, we exposed T47D and MCF-7 breast cancer cell lines to progressively increasing concentrations of tamoxifen or palbociclib over a period of 12 to 24 months, thus generating resistant variants. Firstly, we obtained the tamoxifen-resistant variants (T47D-TR and MCF-7-TR) and palbociclib-resistant variants (T47D-PR and MCF-7-PR). We next used the tamoxifen-resistant variants to generate the double resistant variants (T47D-TPR and MCF-7-TPR), as a means to mimic the treatment sequence used in the clinic. We evaluated the morphology of the resistant variants growing in 2D and found that they display increased cellular atypia compared to their parental lines. They also form irregular and disorganized structures growing in 3D on Geltrex and in suspension as mammospheres, which correlates with an aberrant or reduced E-cadherin expression.Furthermore, the tamoxifen-resistant variant T47D-TR shows increased mammosphere forming capacity, in concordance with higher expression of stemness markers. Moreover, both the tamoxifen-resistant variant MCF-7-TR and the palbociclib-resistant variant MCF-7-PR display enhanced migratory capacity. Regarding cell proliferation, the resistant cell lines show decreased growth rate compared to the parental cell line, both in vitro and in vivo. On the other hand, we found cell cycle proteins such as cyclin D1, cyclin E2, CDK4, CDK6 and CDK1 to be increased in the resistant variants in contrast with their reduced proliferation rates, as well as reduced Rb. Additionally, the resistant variants exhibit lower expression of ER and PR, overactivation of PI3K/AKT/mTOR pathway at the level of AKT or ribosomal protein S6, and higher expression of PKCα than the wild type. We next evaluated the response of these cell lines to different PI3K/AKT/mTOR inhibitors that act at different levels of the pathway. We found that rapamycin (mTOR inhibitor) was more effective in suppressing cell proliferation than alpelisib (PI3K inhibitor). Furthermore, rapamycin and palbociclib combination had a greater effect than each drug used separately in suppressing cell proliferation and tumor growth as well as in reducing cell cycle proteins and PI3K/AKT/mTOR activation. Finally, in order to validate these results, we used patient derived xenografts (PDX) obtained from ER+ breast cancer patients that harbored sensitive or resistant tumors to tamoxifen and palbociclib. We disaggregated the PDXs to obtain single cells which were next grown on Matrigel. We found that most cultures are sensitive to alpelisib (PI3K inhibitor), whereas the totality of PDXs are sensitive to everolimus (mTOR inhibitor), regardless of the presence of mutations or alterations in PI3K/AKT/mTOR pathway. The triple combination of palbociclib with everolimus and fulvestrant (ER inhibitor) is also more effective than each drug separately in reducing cell cycle proteins and PI3K/AKT/mTOR activation. Collectively, our results indicate that combined treatment of palbociclib with mTOR inhibitors is effective in the context of resistance to either tamoxifen or palbociclib by inhibiting cell proliferation and tumor growth as wells as regulating the activation of the cyclin D1/CDK4/6/Rb axis and PI3K/AKT/mTOR pathway. The proposed combination could therefore prevent pathway reactivation downstream mTOR, delaying the development of resistance. In conclusion, in this work we were able to generate and characterize experimental models of acquired resistance to tamoxifen and palbociclib, following the therapeutic sequence used in the clinic. These models are useful to study the mechanisms associated with resistance both in cell culture and in vivo, in order to suggest better therapeutic strategies for patients that relapse to these therapies, as well as contribute to the identification of new biomarkers of therapeutic response.Fil: Rodríguez, María Jimena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

The PHANGS–JWST Treasury Survey: Star Formation, Feedback, and Dust Physics at High Angular Resolution in Nearby GalaxieS

The PHANGS collaboration has been building a reference data set for the multiscale, multiphase study of star formation and the interstellar medium (ISM) in nearby galaxies. With the successful launch and commissioning of JWST, we can now obtain high-resolution infrared imaging to probe the youngest stellar populations and dust emission on the scales of star clusters and molecular clouds (∼5–50 pc). In Cycle 1, PHANGS is conducting an eight-band imaging survey from 2 to 21 μm of 19 nearby spiral galaxies. Optical integral field spectroscopy, CO(2–1) mapping, and UV-optical imaging for all 19 galaxies have been obtained through large programs with ALMA, VLT-MUSE, and Hubble. PHANGS–JWST enables a full inventory of star formation, accurate measurement of the mass and age of star clusters, identification of the youngest embedded stellar populations, and characterization of the physical state of small dust grains. When combined with Hubble catalogs of ∼10,000 star clusters, MUSE spectroscopic mapping of ∼20,000 H II regions, and ∼12,000 ALMA-identified molecular clouds, it becomes possible to measure the timescales and efficiencies of the earliest phases of star formation and feedback, build an empirical model of the dependence of small dust grain properties on local ISM conditions, and test our understanding of how dust-reprocessed starlight traces star formation activity, all across a diversity of galactic environments. Here we describe the PHANGS–JWST Treasury survey, present the remarkable imaging obtained in the first few months of science operations, and provide context for the initial results presented in the first series of PHANGS–JWST publications.La lista completa de autores que integran el documento puede consultarse en el archivo.Instituto de Astrofísica de La Plat

PHANGS–JWST First Results: Massive Young Star Clusters and New Insights from JWST Observations of NGC1365

A primary new capability of JWST is the ability to penetrate the dust in star-forming galaxies to identify and study the properties of young star clusters that remain embedded in dust and gas. In this Letter we combine new infrared images taken with JWST with our optical Hubble Space Telescope (HST) images of the starbursting barred (Seyfert2) spiral galaxy NGC 1365. We find that this galaxy has the richest population of massive young clusters of any known galaxy within 30 Mpc, with ∼30 star clusters that are more massive than 106Me and younger than 10 Myr. Sixteen of these clusters are newly discovered from our JWST observations. An examination of the optical images reveals that 4 of 30 (∼13%) are so deeply embedded that they cannot be seen in the Hubble I band (AV 10 mag), and that 11 of 30 (∼37%) are missing in the HST B band, so age and mass estimates from optical measurements alone are challenging. These numbers suggest that massive clusters in NGC 1365 remain completely obscured in the visible for ∼1.3 ± 0.7 Myr and are either completely or partially obscured for ∼3.7 ± 1.1 Myr. We also use the JWST observations to gain new insights into the triggering of star cluster formation by the collision of gas and dust streamers with gas and dust in the bar. The JWST images reveal previously unknown structures (e.g., bridges and overshoot regions from stars that form in the bar) that help us better understand the orbital dynamics of barred galaxies and associated star-forming rings. Finally, we note that the excellent spatial resolution of the NIRCAM F200W filter provides a better way to separate barely resolved compact clusters from individual stars based on their sizes.La lista completa de autores que integran el documento puede consultarse en el archivo.Instituto de Astrofísica de La Plat

PHANGS–JWST First Results: Dust-embedded Star Clusters in NGC 7496 Selected via 3.3μm PAH Emission

The earliest stages of star formation occur enshrouded in dust and are not observable in the optical. Here we leverage the extraordinary new high-resolution infrared imaging from JWST to begin the study of dust-embedded star clusters in nearby galaxies throughout the Local Volume. We present a technique for identifying dustembedded clusters in NGC 7496 (18.7 Mpc), the first galaxy to be observed by the PHANGS–JWST Cycle 1 Treasury Survey. We select sources that have strong 3.3 μm PAH emission based on a F300M − F335M color excess and identify 67 candidate embedded clusters. Only eight of these are found in the PHANGS-HST optically selected cluster catalog, and all are young (six have SED fit ages of ∼1 Myr). We find that this sample of embedded cluster candidates may significantly increase the census of young clusters in NGC 7496 from the PHANGS-HST catalog; the number of clusters younger than ∼2 Myr could be increased by a factor of 2. Candidates are preferentially located in dust lanes and are coincident with the peaks in the PHANGS-ALMA CO (2–1) maps. We take a first look at concentration indices, luminosity functions, SEDs spanning from 2700 Å to 21 μm, and stellar masses (estimated to be between ∼10⁴ and 10⁵ M☉). The methods tested here provide a basis for future work to derive accurate constraints on the physical properties of embedded clusters, characterize the completeness of cluster samples, and expand analysis to all 19 galaxies in the PHANGS–JWST sample, which will enable basic unsolved problems in star formation and cluster evolution to be addressed.La lista completa de autores que integran el documento puede consultarse en el archivo.Instituto de Astrofísica de La Plat

Factores de riesgo psicosociales que afectan a los docentes que laboran con niños con necesidades educativas especiales (NEE)

La investigación tuvo como propósitodeterminar los factores de riesgo psicosocialesque afectan a los docentes que laboran con niñoscon necesidades educativas especiales (NEE),en la Institución Educativa CEINAR de Neiva.El trabajo se desarrolló bajo el paradigma deinvestigación cuantitativa, que empleó la bateríade evaluación de riesgos psicosociales delMinisterio de Trabajo y la Pontificia UniversidadJaveriana, elaborada en el 2010, a través de lacual, se recolectó la información requerida paraevaluar las condiciones psicosociales

Identification and analysis of the young population in the starburst galaxy NGC 253

We present a study of the young population in the starburst galaxy NGC 253. In particular, we focused our attention on searching young star groups, obtaining their main properties and studying their hierarchical organization. For this task, we used multiband images and their corresponding photometric data obtained with the Advanced Camera for Surveys of the Hubble Space Telescope (ACS/HST).We have first derived the absorption affecting the different regions of the galaxy. Then, we applied an automatic and objective searching method over the corrected data in order to detect young star groups. We complemented this result with the construction of the stellar density map for the blue young population. A statistical procedure to decontaminate the photometric diagrams from field stars was applied over the detected groups and we estimated their fundamental parameters.As a result, we built a catalog of 875 new identified young groups with their main characteristics, including coordinates, sizes, estimated number of members, stellar densities, luminosity function (LF) slopes and galactocentric distances. We observed these groups delineate different structures of the galaxy, and they are the last step in the hierarchical way in which the young population is organized. From their size distribution, we found they have typical radius of ∼ 40 − 50 pc. These values are consistent with those ones found in others nearby galaxies. We estimated a mean value of the LF slope of 0.21 and an average density of 0.0006 stars/pc³ for the identified young groups taking into account stars earlier than B6.Instituto de Astrofísica de La Plat