Natural killer (NK) cell-derived extracellular-vesicle shuttled microRNAs control T cell responses.

Natural killer (NK) cells recognize and kill target cells undergoing different types of stress. NK cells are also capable of modulating immune responses. In particular, they regulate T cell functions. Small RNA next-generation sequencing of resting and activated human NK cells and their secreted extracellular vesicles (EVs) led to the identification of a specific repertoire of NK-EV-associated microRNAs and their post-transcriptional modifications signature. Several microRNAs of NK-EVs, namely miR-10b-5p, miR-92a-3p, and miR-155-5p, specifically target molecules involved in Th1 responses. NK-EVs promote the downregulation of GATA3 mRNA in CD4+ T cells and subsequent TBX21 de-repression that leads to Th1 polarization and IFN-γ and IL-2 production. NK-EVs also have an effect on monocyte and moDCs (monocyte-derived dendritic cells) function, driving their activation and increased presentation and costimulatory functions. Nanoparticle-delivered NK-EV microRNAs partially recapitulate NK-EV effects in mice. Our results provide new insights on the immunomodulatory roles of NK-EVs that may help to improve their use as immunotherapeutic tools.This manuscript was funded by grants PDI-2020-120412RB-I00 and PDC2021- 121719-I00 (FS-M) and PID2020- 119352RB-I00 (AS) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M). CIBERCV (CB16/11/00272) and BIOIMID PIE13/041 from the Instituto de Salud Carlos. The current research has received funding from 'la Caixa' Foundation under the project code HR17-00016. Grants from Ramón Areces Foundation 'Ciencias de la Vida y de la Salud' (XIX Concurso-2018) and from Ayuda Fundación BBVA y Equipo de Investigación Científica (BIOMEDICINA-2018) (to FSM). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505). IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, CEX2020-001039-S). SGD is supported by a grant from the Spanish Ministry of Universities. Authors thank Dr Miguel Vicente-Manzanares for critical review and editing. We also thank Dr Francisco Urbano and Dr Covadonga Aguado for their support with EM (TEM facilities, Universidad Autónoma de Madrid).S

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&

Mechanisms of coronavirus pathogenicity and virus-host interactions

Trabajo presentado en la Conference on the Cooperation and Collaboration on Prevention and Control of Animal Diseases, celebrada en Hangzhou (China), del 21 al 23 de mayo de 2019Coronaviruses (CoVs) are important human and animal pathogens mainly causing respiratory and enteric infections with diverse severity. The presence of CoVs in bats, as animal reservoirs, and their ability for interspecies transmission have recently led to the emergence of novel CoVs responsible for epidemics in humans and livestock. In order to develop protection strategies against CoV infections, our laboratory is interested in the identification of (i) Viral factors involved in virulence and (ii) Host signaling pathways contributing to pathogenesis, using human coronaviruses SARS- and MERS-CoVs as model systems

Event‐scale dynamics of a parabolic dune and its relevance for mesoscale evolution

Parabolic dunes are wide-spread aeolian landforms found in a variety of environments. Despite modelling advances and good understanding of how they evolve, there is limited empirical data on their dynamics at short time-scales of hours, and on how these dynamics relate to their medium-term evolution. This study presents the most comprehensive dataset to date on aeolian processes (airflow and sediment transport) inside a parabolic dune at an event-scale. This is coupled with information on elevation changes inside the landform to understand its morphological response to a single wind event. Results are contextualized against the medium-term (years) allowing us to investigate one of the most persistent conundrums in geomorphology, that of the significance of short-term findings for landform evolution. Our field data suggested three key findings: 1) sediment transport rates inside parabolic dunes correlate well with wind speeds rather than turbulence; 2) up to several tonnes of sand can move through these landforms in a few hours; 3) short-term elevation changes inside parabolic dunes can be complex and different from long-term net spatial patterns, including simultaneous erosion and accumulation along the same wall. Modeled airflow patterns along the basin were similar to those measured in situ for a range of common wind directions, demonstrating the potential for strong transport during multiple events. Meso-scale analyses suggested that the measured event was representative of the type of events potentially driving significant geomorphic changes over years, with supply-limiting conditions playing an important role in resultant flux amounts

Dynamic molecular mechanism of the nuclear pore complex permeability barrier

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport of specific macromolecules while impeding the exchange of unsolicited material. However, key aspects of this gating mechanism remain controversial. To address this issue, we determined the nanoscopic behavior of the permeability barrier directly within yeast S. cerevisiae NPCs at transport-relevant timescales. We show that the large intrinsically disordered domains of phenylalanine-glycine repeat nucleoporins (FG Nups) exhibit highly dynamic fluctuations to create transient voids in the permeability barrier that continuously shape-shift and reseal, resembling a radial polymer brush. Together with cargo-carrying transport factors the FG domains form a feature called the central plug, which is also highly dynamic. Remarkably, NPC mutants with longer FG domains show interweaving meshwork-like behavior that attenuates nucleocytoplasmic transport in vivo. Importantly, the bona fide nanoscale NPC behaviors and morphologies are not recapitulated by in vitro FG domain hydrogels. NPCs also exclude self-assembling FG domain condensates in vivo, thereby indicating that the permeability barrier is not generated by a self-assembling phase condensate, but rather is largely a polymer brush, organized by the NPC scaffold, whose dynamic gating selectivity is strongly enhanced by the presence of transport factors.</p

Lyman break and UV-selected galaxies at z ~ 1: II. PACS-100um/160um FIR detections

We report the PACS-100um/160um detections of a sample of 42 GALEX-selected and FIR-detected Lyman break galaxies (LBGs) at z ~ 1 located in the COSMOS field and analyze their ultra-violet (UV) to far-infrared (FIR) properties. The detection of these LBGs in the FIR indicates that they have a dust content high enough so that its emission can be directly detected. According to a spectral energy distribution (SED) fitting with stellar population templates to their UV-to-near-IR observed photometry, PACS-detected LBGs tend to be bigger, more massive, dustier, redder in the UV continuum, and UV-brighter than PACS-undetected LBGs. PACS-detected LBGs at z ~ 1 are mostly disk-like galaxies and are located over the green-valley and red sequence of the color-magnitude diagram of galaxies at their redshift. By using their UV and IR emission, we find that PACS-detected LBGs tend to be less dusty and have slightly higher total star-formation rates (SFRs) than other PACS-detected UV-selected galaxies within their same redshift range. As a consequence of the selection effect due to the depth of the FIR observations employed, all our PACS-detected LBGs are LIRGs. However, none of them are in the ULIRG regime, where the FIR observations are complete. The finding of ULIRGs-LBGs at higher redshifts suggests an evolution of the FIR emission of LBGs with cosmic time. In an IRX-$\beta$ diagram, PACS-detected LBGs at z ~ 1 tend to be located around the relation for local starburst similarly to other UV-selected PACS-detected galaxies at their same redshift. Consequently, the dust-correction factors obtained with their UV continuum slope allow to determine their total SFR, unlike at higher redshifts. However, the dust attenuation derived from UV to NIR SED fitting overestimates the total SFR for most of our PACS-detected LBGs in age-dependent way: the overestimation factor is higher in younger galaxies.Comment: Accepted for publication in MNRA

MAGIC upper limits on the very high energy emission from GRBs

The fast repositioning system of the MAGIC Telescope has allowed during its first data cycle, between 2005 and the beginning of year 2006, observing nine different GRBs as possible sources of very high energy gammas. These observations were triggered by alerts from Swift, HETE-II, and Integral; they started as fast as possible after the alerts and lasted for several minutes, with an energy threshold varying between 80 and 200 GeV, depending upon the zenith angle of the burst. No evidence for gamma signals was found, and upper limits for the flux were derived for all events, using the standard analysis chain of MAGIC. For the bursts with measured redshift, the upper limits are compatible with a power law extrapolation, when the intrinsic fluxes are evaluated taking into account the attenuation due to the scattering in the Metagalactic Radiation Field (MRF).Comment: 25 pages, 9 figures, final version accepted by ApJ. Changet title to "MAGIC upped limits on the VERY high energy emission from GRBs", re-organized chapter with description of observation, removed non necessaries figures, added plot of effective area depending on zenith angle, added an appendix explaining the upper limit calculation, added some reference