Hipoplasia tímica en pacientes pediátricos con enfermedad respiratoria

Objective: To determine the clinical and epidemiologic features of children with thymic hypoplasia and respiratory illnesses in Cuba. Methods: A retrospective study was conducted among children of 1-6 years of age of both sexes attended at a Pediatric Immunology Program of Hospital Materno Infantil Ángel Arturo Aballí Arellano in Habana, Cuba from September 2019 to August 2022. Children with thymic hypoplasia with and without a history of a respiratory illness either infectious or non-infectious were included.Results: No association between age andsex with thymic hypoplasia but an association was found with children with a severe respiratory illness. Factors associated with a severe respiratory illness were ineffective breastfeeding, history of an atopic condition, pregnancy of high risk, prematurity and exposure to tobacco smoke. Conclusions:Thymic hypoplasia was not associated with age or sex. An association with mild-moderate thymic hypoplasia was found with a severe respiratory illness.Objetivos: Determinar las características clínicas y epidemiológicas de niños con hipoplasia del timo y enfermedad respiratoria en Cuba. Material y Métodos: Estudio descriptivo retrospectivo en niños con edades comprendidas entre 1 y 6 años, de ambos sexos, atendidos en la consulta de Inmunología Pediátrica del Programa de Proyección Comunitaria del Municipio Arroyo Naranjo de La Habana o en la consulta de Inmunología Pediátrica del Hospital Materno Infantil Ángel Arturo Aballí Arellano del Municipio Arroyo Naranjo La Habana, entre los meses de septiembre 2019 y agosto 2022. Se incluyeron los niños con hipoplasia tímica y con antecedentes personales de enfermedad respiratoria infecciosa o no infecciosa diagnosticadas durante el período de estudio. Resultados: No se encontró relación entre la hipoplasia tímica y la edad o el sexo; se encontró mayor frecuencia de la hipoplasia tímica leve y moderada en niños con desarrollo de enfermedad respiratoria grave. Los factores con mayor frecuencia descritos en la enfermedad respiratoria complicada fueron la lactancia materna inefectiva, los antecedentes patológicos personales de atopia, el embarazode riesgo, la prematuridad, el humo de tabaco en el ambiente y la asistencia a círculo infantil o a casa de cuidado infantil. Conclusiones: El desarrollo de hipoplasia tímica no mostró relación con la edad y el sexo. Se describieron varias condiciones con mayor frecuencia en niños con hipoplasia tímica y con enfermedad respiratoria complicada.La frecuencia de la hipoplasia tímica leve y moderada fue mayor en los pacientes con enfermedad respiratoria grave

Membrane-to-Nucleus Signaling in Human Blood Progenitor Cells Reveals an Efficient GM-Free Reprogramming to Pluripotency

The generation of induced pluripotent stem cells (iPSCs) by forced expression of defined transcription factors has revolutionized regenerative medicine. These cells have similar features to embryonic stem cells (ESCs) regarding self-renewal and their ability to differentiate into any cell type in the body. In spite of many improvements, in using nonviral delivery reprogramming methods, there are still challenges to overcome regarding safety before patient-made iPSCs can be used in regular clinical practice. We have recently reported about a gene manipulation-free method of generating human pluripotent stem cells (PSCs), based on activation of the novel human GPI-linked glycoprotein ACA. The process of dedifferentiation of blood progenitor cells that leads to the generation of blood-derived pluripotent stem cells (BD-PSCs) is initiated upon cross-linking of this protein via activation of PLCγ/PI3K/Akt pathway. These cells are mortal, express pluripotent markers, and redifferentiate in vitro into cells of all three germ layers. The ultrastructural analysis of BD-PSCs, by means of electron microscopy, revealed them similar to human ESCs with large dense nucleolus and scarce cytoplasm. BD-PSCs are autologous stem cells and while nonteratogenic offer a new alternative that overcomes immunological, ethical, and safety concerns and opens up a new avenue in treating contemporarily intractable diseases and generally in human therapeutics

Correlated Alterations in Serotonergic and Dopaminergic Modulations at the Hippocampal Mossy Fiber Synapse in Mice Lacking Dysbindin

Dysbindin-1 (dystrobrevin-binding protein 1, DTNBP1) is one of the promising schizophrenia susceptibility genes. Dysbindin protein is abundantly expressed in synaptic regions of the hippocampus, including the terminal field of the mossy fibers, and this hippocampal expression of dysbindin is strongly reduced in patients with schizophrenia. In the present study, we examined the functional role of dysbindin in hippocampal mossy fiber-CA3 synaptic transmission and its modulation using the sandy mouse, a spontaneous mutant with deletion in the dysbindin gene. Electrophysiological recordings were made in hippocampal slices prepared from adult male sandy mice and their wild-type littermates. Basic properties of the mossy fiber synaptic transmission in the mutant mice were generally normal except for slightly reduced frequency facilitation. Serotonin and dopamine, two major neuromodulators implicated in the pathophysiology of schizophrenia, can potentiate mossy fiber synaptic transmission probably via an increase in cAMP levels. Synaptic potentiation induced by serotonin and dopamine was very variable in magnitude in the mutant mice, with some mice showing prominent enhancement as compared with the wild-type mice. In addition, the magnitude of potentiation induced by these monoamines significantly correlated with each other in the mutant mice, indicating that a subpopulation of sandy mice has marked hypersensitivity to both serotonin and dopamine. While direct activation of the cAMP cascade by forskolin induced robust synaptic potentiation in both wild-type and mutant mice, this forskolin-induced potentaition correlated in magnitude with the serotonin-induced potentiation only in the mutant mice, suggesting a possible change in coupling of receptor activation to downstream signaling. These results suggest that the dysbindin deficiency could be an essential genetic factor that causes synaptic hypersensitivity to dopamine and serotonin. The altered monoaminergic modulation at the mossy fiber synapse could be a candidate pathophysiological basis for impairment of hippocampus-dependent brain functions in schizophrenia

Furiously fast and red: sub-second optical flaring in V404 Cyg during the 2015 outburst peak

We present observations of rapid (sub-second) optical flux variability in V404 Cyg during its 2015 June outburst. Simultaneous three-band observations with the ULTRACAM fast imager on four nights show steep power spectra dominated by slow variations on ∼100–1000 s time-scales. Near the peak of the outburst on June 26, a dramatic change occurs and additional, persistent sub-second optical flaring appears close in time to giant radio and X-ray flaring. The flares reach peak optical luminosities of ∼ few × 1036 erg s−1. Some are unresolved down to a time resolution of 24 ms. Whereas the fast flares are stronger in the red, the slow variations are bluer when brighter. The redder slopes, emitted power and characteristic time-scales of the fast flares can be explained as optically thin synchrotron emission from a compact jet arising on size scales ∼140–500 Gravitational radii (with a possible additional contribution by a thermal particle distribution). The origin of the slower variations is unclear. The optical continuum spectral slopes are strongly affected by dereddening uncertainties and contamination by strong Hα emission, but the variations of these slopes follow relatively stable loci as a function of flux. Cross-correlating the slow variations between the different bands shows asymmetries on all nights consistent with a small red skew (i.e. red lag). X-ray reprocessing and non-thermal emission could both contribute to these. These data reveal a complex mix of components over five decades in time-scale during the outburst

The CARMENES search for exoplanets around M dwarfs High-resolution optical and near-infrared spectroscopy of 324 survey stars

The CARMENES radial velocity (RV) survey is observing 324 M dwarfs to search for any orbiting planets. In this paper, we present the survey sample by publishing one CARMENES spectrum for each M dwarf. These spectra cover the wavelength range 520–1710 nm at a resolution of at least R >80 000, and we measure its RV, Hα emission, and projected rotation velocity. We present an atlas of high-resolution M-dwarf spectra and compare the spectra to atmospheric models. To quantify the RV precision that can be achieved in low-mass stars over the CARMENES wavelength range, we analyze our empirical information on the RV precision from more than 6500 observations. We compare our high-resolution M-dwarf spectra to atmospheric models where we determine the spectroscopic RV information content, Q, and signal-to-noise ratio. We find that for all M-type dwarfs, the highest RV precision can be reached in the wavelength range 700–900 nm. Observations at longer wavelengths are equally precise only at the very latest spectral types (M8 and M9). We demonstrate that in this spectroscopic range, the large amount of absorption features compensates for the intrinsic faintness of an M7 star. To reach an RV precision of 1 m s−1 in very low mass M dwarfs at longer wavelengths likely requires the use of a 10 m class telescope. For spectral types M6 and earlier, the combination of a red visual and a near-infrared spectrograph is ideal to search for low-mass planets and to distinguish between planets and stellar variability. At a 4 m class telescope, an instrument like CARMENES has the potential to push the RV precision well below the typical jitter level of 3–4 m s−1

The CARMENES search for exoplanets around M dwarfs. Two temperate Earth-mass planet candidates around Teegarden’s Star

Context.Teegarden’s Star is the brightest and one of the nearest ultra-cool dwarfs in the solar neighbourhood. For its late spectral type (M7.0 V),the star shows relatively little activity and is a prime target for near-infrared radial velocity surveys such as CARMENES.Aims.As part of the CARMENES search for exoplanets around M dwarfs, we obtained more than 200 radial-velocity measurements of Teegarden’sStar and analysed them for planetary signals.Methods.We find periodic variability in the radial velocities of Teegarden’s Star. We also studied photometric measurements to rule out stellarbrightness variations mimicking planetary signals.Results.We find evidence for two planet candidates, each with 1.1M⊕minimum mass, orbiting at periods of 4.91 and 11.4 d, respectively. Noevidence for planetary transits could be found in archival and follow-up photometry. Small photometric variability is suggestive of slow rotationand old age.Conclusions.The two planets are among the lowest-mass planets discovered so far, and they are the first Earth-mass planets around an ultra-cooldwarf for which the masses have been determined using radial velocities.We thank the referee Rodrigo Díaz for a careful review andhelpful comments. M.Z. acknowledges support from the Deutsche Forschungs-gemeinschaft under DFG RE 1664/12-1 and Research Unit FOR2544 “BluePlanets around Red Stars”, project no. RE 1664/14-1. CARMENES isan instrument for the Centro Astronómico Hispano-Alemán de Calar Alto(CAHA, Almería, Spain). CARMENES is funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de InvestigacionesCientíficas (CSIC), the European Union through FEDER/ERF FICTS-2011-02 funds, and the members of the CARMENES Consortium (Max-Planck-Institut für Astronomie, Instituto de Astrofísica de Andalucía, LandessternwarteKönigstuhl, Institut de Ciències de l’Espai, Institut für Astrophysik Göttingen,Universidad Complutense de Madrid, Thüringer Landessternwarte Tautenburg,Instituto de Astrofísica de Canarias, Hamburger Sternwarte, Centro de Astro-biología and Centro Astronómico Hispano-Alemán), with additional contribu-tions by the Spanish Ministry of Economy, the German Science Foundationthrough the Major Research Instrumentation Programme and DFG ResearchUnit FOR2544 “Blue Planets around Red Stars”, the Klaus Tschira Stiftung, thestates of Baden-Württemberg and Niedersachsen, and by the Junta de Andalucía.Based on data from the CARMENES data archive at CAB (INTA-CSIC). Thisarticle is based on observations made with the MuSCAT2 instrument, devel-oped by ABC, at Telescopio Carlos Sánchez operated on the island of Tener-ife by the IAC in the Spanish Observatorio del Teide. Data were partly col-lected with the 150-cm and 90-cm telescopes at the Sierra Nevada Observa-tory (SNO) operated by the Instituto de Astrofísica de Andalucía (IAA-CSIC).Data were partly obtained with the MONET/South telescope of the MOnitoringNEtwork of Telescopes, funded by the Alfried Krupp von Bohlen und HalbachFoundation, Essen, and operated by the Georg-August-Universität Göttingen,the McDonald Observatory of the University of Texas at Austin, and the SouthAfrican Astronomical Observatory. We acknowledge financial support from theSpanish Agencia Estatal de Investigación of the Ministerio de Ciencia, Inno-vación y Universidades and the European FEDER/ERF funds through projectsAYA2015-69350-C3-2-P, AYA2016-79425-C3-1/2/3-P, AYA2018-84089, BES-2017-080769, BES-2017-082610, ESP2015-65712-C5-5-R, ESP2016-80435-C2-1/2-R, ESP2017-87143-R, ESP2017-87676-2-2, ESP2017-87676-C5-1/2/5-R, FPU15/01476, RYC-2012-09913, the Centre of Excellence ”Severo Ochoa”and ”María de Maeztu” awards to the Instituto de Astrofísica de Canarias (SEV-2015-0548), Instituto de Astrofísica de Andalucía (SEV-2017-0709), and Cen-tro de Astrobiología (MDM-2017-0737), the Generalitat de Catalunya throughCERCA programme”, the Deutsches Zentrum für Luft- und Raumfahrt throughgrants 50OW0204 and 50OO1501, the European Research Council through grant694513, the Italian Ministero dell’instruzione, dell’università de della ricerca andUniversità degli Studi di Roma Tor Vergata through FFABR 2017 and “Mis-sion: Sustainability 2016”, the UK Science and Technology Facilities Council through grant ST/P000592/1, the Israel Science Foundation through grant848/16, the Chilean CONICYT-FONDECYT through grant 3180405, the Mexi-can CONACYT through grant CVU 448248, the JSPS KAKENHI through grantsJP18H01265 and 18H05439, and the JST PRESTO through grant JPMJPR1775

The CARMENES search for exoplanets around M dwarfs HD147379 b: A nearby Neptune in the temperate zone of an early-M dwarf

We report on the first star discovered to host a planet detected by radial velocity (RV) observations obtained within the CARMENES survey for exoplanets around M dwarfs. HD 147379 (V = 8.9 mag, M = 0.58 ± 0.08 M⊙), a bright M0.0 V star at a distance of 10.7 pc, is found to undergo periodic RV variations with a semi-amplitude of K = 5.1 ± 0.4 m s−1 and a period of P = 86.54 ± 0.06 d. The RV signal is found in our CARMENES data, which were taken between 2016 and 2017, and is supported by HIRES/Keck observations that were obtained since 2000. The RV variations are interpreted as resulting from a planet of minimum mass mP sin i = 25 ± 2 M⊕, 1.5 times the mass of Neptune, with an orbital semi-major axis a = 0.32 au and low eccentricity (e < 0.13). HD 147379 b is orbiting inside the temperate zone around the star, where water could exist in liquid form. The RV time-series and various spectroscopic indicators show additional hints of variations at an approximate period of 21.1 d (and its first harmonic), which we attribute to the rotation period of the star.FEDER/ERF FICTS-2011-02 fundsMajor Research Instrumentation Programme and DFG Research Unit FOR2544 “Blue Planets around Red StarsEuropean Research Council (ERC-279347), Deutsche Forschungsgemeinschaft (RE 1664/12-1, RE 2694/4-1), Bundesministerium für Bildung und Forschung (BMBF-05A14MG3, BMBF-05A17MG3), Spanish Ministry of Economy and Competitiveness (MINECO, grants AYA2015-68012-C2-2-P, AYA2016-79425-C3-1,2,3-P, AYA2015-69350-C3-2-P, AYA2014-54348-C03- 01, AYA2014-56359-P, AYA2014-54348-C3-2-R, AYA2016-79425-C3-3-P and 2013 Ramòn y Cajal program RYC-2013-14875), Fondo Europeo de Desarrollo Regional (FEDER, grant ESP2016-80435-C2-1-R, ESP2015-65712-C5- 5-R), Generalitat de Catalunya/CERCA programme, Spanish Ministerio de Educación, Cultura y Deporte, programa de Formación de Profesorado Universitario (grant FPU15/01476), Deutsches Zentrum für Luft- und Raumfahrt (grants 50OW0204 and 50OO1501), Office of Naval Research Global (award no. N62909-15-1-2011), Mexican CONACyT grant CB-2012-183007

The CARMENES search for exoplanets around M dwarfs. First visual-channel radial-velocity measurements and orbital parameter updates of seven M-dwarf planetary systems

Stars and planetary system