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The controlled delivery of nucleic acids to selected tissues remains an inefficient process mired by low transfection efficacy, poor scalability because of varying efficiency with cell type and location, and questionable safety as a result of toxicity issues arising from the typical materials and procedures employed. High efficiency and minimal toxicity in vitro has been shown for intracellular delivery of nuclei acids by using nanoneedles, yet extending these characteristics to in vivo delivery has been difficult, as current interfacing strategies rely on complex equipment or active cell internalization through prolonged interfacing. Here, we show that a tunable array of biodegradable nanoneedles fabricated by metal-assisted chemical etching of silicon can access the cytosol to co-deliver DNA and siRNA with an efficiency greater than 90%, and that in vivo the nanoneedles transfect the VEGF-165 gene, inducing sustained neovascularization and a localized sixfold increase in blood perfusion in a target region of the muscle. Efficient in vivo cytosolic delivery of nucleic acids through cell-membrane puncturing by an array of biodegradable silicon nanoneedles induces sustained local neovascularization in muscle.

The margination dynamics of microparticles with different shapes has been analyzed within a laminar flow mimicking the hydrodynamic conditions in the microcirculation. Silica spherical particles, quasi-hemispherical and discoidal silicon particles have been perfused in a parallel plate flow chamber. The effect of the shape and density on their margination propensity has been investigated at different physiologically relevant shear rates S. Simple scaling laws have been derived showing that the number n of marginating particles scales as S - 0.63 for the spheres; S - 0.85 for discoidal and S - 1 for quasi-hemispherical particles, regardless of their density and size. Within the range considered for the shear rate, discoidal particles marginate in a larger number compared to quasi-hemispherical and spherical particles. These results may be of interest in drug delivery and bio-imaging applications, where particles are expected to drift towards and interact with the walls of the blood vessels.

The epicardium constitutes an untapped reservoir for cardiac regeneration. Upon heart injury, the adult epicardium re-activates, leading to epithelial-to-mesenchymal transition (EMT), migration, and differentiation. While interesting mechanistic and therapeutic findings arose from lower vertebrates and rodent models, the introduction of an experimental system representative of large mammals would undoubtedly facilitate translational advancements. Here, we apply innovative protocols to obtain living 3D organotypic epicardial slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve the in vivo architecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon thymosin β4 treatment of the slices, the epicardial cells become activated, upregulating epicardial and EMT genes, resulting in epicardial cell mobilization and differentiation into epicardial-derived mesenchymal cells. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering an advanced tool to explore ex vivo the complex 3D interactions occurring within the native heart environment.

We present recent results from the Pristine Inner Galaxy Survey (PIGS), which used metallicity-sensitive narrow-band CaHK photometry to identify and follow up spectroscopically thousands of ancient metal-poor candidates in the bulge. For the spectroscopic PIGS sample, we derive distances with StarHorse and compute orbital properties in a realistic potential including a bar. We find that a significant fraction of metal-poor stars is confined to the inner Galaxy (apocentre < 4 kpc), with an estimated confined fraction of 80%/50% at [Fe/H] = − 1.0/ − 2.0. We also find that the very metal-poor population has a net prograde rotation, with a υ ϕ ∼ 40 kms −1 . It is still under discussion what the origin is of the population of very metal-poor inner Galaxy stars – it is likely a combination of in-situ and accreted stars. In future, spectroscopic observations from 4MOST will be crucial to complete our picture.

Radial metallicity gradients measured today in the interstellar medium (ISM) and stellar components of disk galaxies are the result of chemo-dynamical evolution since the beginning of disk formation. This makes it difficult to infer the disk past without knowledge of the ISM metallicity gradient evolution with cosmic time. We show that abundance gradients are meaningful only if stellar age information is available. The observed gradient inversion with distance from the disk mid-plane seen in the Milky Way can be explained as the effect of inside-out disk formation and disk flaring of mono-age populations. A novel recent method is presented for constraining the evolution of the Galactic ISM metallicity with radius and time directly from the observations, while at the same time recovering the birth radii of any stellar sample with precise metallicity and age measurements.

The standard cosmological model predicts that galaxies are built through hierarchical assembly on cosmological timescales 1 , 2 . The Milky Way, like other disk galaxies, underwent violent mergers and accretion of small satellite galaxies in its early history. Owing to Gaia Data Release 2 3 and spectroscopic surveys 4 , the stellar remnants of such mergers have been identified 5 – 7 . The chronological dating of such events is crucial to uncover the formation and evolution of the Galaxy at high redshift, but it has so far been challenging due to difficulties in obtaining precise ages for these oldest stars. Here we combine asteroseismology—the study of stellar oscillations—with kinematics and chemical abundances to estimate precise stellar ages (~11%) for a sample of stars observed by the Kepler space mission 8 . Crucially, this sample includes not only some of the oldest stars that were formed inside the Galaxy but also stars formed externally and subsequently accreted onto the Milky Way. Leveraging this resolution in age, we provide compelling evidence in favour of models in which the Galaxy had already formed a substantial population of its stars (which now reside mainly in its thick disk) before the infall of the satellite galaxy Gaia-Enceladus/Sausage 5 , 6 around 10 billion years ago. Leveraging asteroseismology, stellar abundances and kinematics to derive precise ages for a sample of 95 stars, Montalbán et al. determine that the Milky Way was already host to a substantial population of stars when it was just 3.8 billion years old, at the time of the Gaia-Enceladus accretion event.

4MOST is a new wide-field, high-multiplex spectroscopic survey facility for the VISTA telescope of ESO. Starting in 2022, 4MOST will deploy 2400 fibres in a 4.1 square degree field-of-view using a positioner based on the tilting spine principle. In this contribution we give an outline of the major science goals we wish to achieve with 4MOST in the area of Galactic Archeology. The 4MOST Galactic Archeology surveys have been designed to address long-standing and far-reaching problems in Galactic science. They are focused on four major themes: 1) Near-field cosmology tests, 2) Chemo-dynamical characterisation of the major Milky Way stellar components, 3) The Galactic Halo and beyond, and 4) Discovery and characterisation of extremely metal-poor stars. In addition to a top-level description of the Galactic surveys we provide information about how the community will be able to join 4MOST via a call for Public Spectroscopic Surveys that ESO will launch.

The observational constraints are of fundamental importance to build a realistic chemical evolution model. With respect to these constraints the last years have been of crucial importance and, in the case of the Milky Way, the new observational data required a revision of the previous chemical evolution models (see Chiappini et al., 1997 - CMG97) and Pagel and Tautvaisiene, 1995 - PT95). The results obtained by CMG97 from a careful comparison between model predictions and observational constraints strongly suggest that the previously adopted picture for the Galaxy formation in which the gas shed from the halo was the main contributor to the thin disk formation, is not valid anymore. With our detailed chemical evolution model we are able to put some constraints on the IMF variation and on the Deuterium primordial value.