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A study monitoring the brightness of stars in the Large Magellanic Cloud observed two possible microlensing events. Evidence indicates that the masses of lensing objects are equal to one solar mass or less.

Candidate pre-main-sequence stars were observed in the bar of the Large Magellanic Cloud during the search for dark matter in the galactic halo. Seven blue stars of apparent visual magnitude 15 to 17 had irregular photometric variations and hydrogen emission lines in their optical spectra, which suggested that these stars are pre-main-sequence stars of about 10 solar masses. These stars are slightly more massive and definitely more luminous than are Herbig AeBe pre-main-sequence stars in our own galaxy. Continued observations of these very young stars from another galaxy, which are probably at the pre-hydrogen-burning stage, should provide important clues about early stages of star formation.

The magnetopause is the boundary between the interplanetary magnetic field and the terrestrial magnetic field. It is influenced by different solar-wind conditions, which lead to a change in the shape and location of the magnetopause. The interaction between the solar wind and the magnetosphere can be studied from in situ spacecraft observations. Many studies focus on the equatorial plane as this is where recent spacecraft constellations such as THEMIS or MMS operate. However, to fully capture the interaction, it is important to study the high-latitude regions as well. Since the Cluster spacecraft operate in a highly elliptical polar orbit, the spacecraft often pass through the magnetopause at high latitudes. This allows us to collect a dataset of high-latitude magnetopause crossings and to study magnetopause motion in this region, as well as deviations from established magnetopause models. We use multi-spacecraft analysis tools to investigate the direction of the magnetopause motion in the high latitudes and to compare the occurrence of crossings at different locations with the result in the equatorial plane. We find that the high-latitude magnetopause motion is generally consistent with previously reported values and seems to be more often associated with a closed magnetopause boundary. We show that, on average, the magnetopause moves faster inwards than outwards. Furthermore, the occurrence of magnetopause positions beyond those predicted by the Shue et al. (1998) model at high latitudes is found to be caused by the solar-wind parameters that are similar to those in the equatorial plane. Finally, we highlight the importance of the dipole tilt angle at high latitudes. Our results may be useful for the interpretation of plasma measurements from the upcoming SMILE mission (Branduardi-Raymont et al., 2018) as this spacecraft will also fly frequently through the high-latitude magnetopause.

Plasmodesmata are remarkable cellular machines responsible for the controlled exchange of proteins, small RNAs and signalling molecules between cells. They are lined by the plasma membrane (PM), contain a strand of tubular endoplasmic reticulum (ER), and the space between these two membranes is thought to control plasmodesmata permeability. Here, we have reconstructed plasmodesmata three-dimensional (3D) ultrastructure with an unprecedented level of 3D information using electron tomography. We show that within plasmodesmata, ER–PM contact sites undergo substantial remodelling events during cell differentiation. Instead of being open pores, post-cytokinesis plasmodesmata present such intimate ER–PM contact along the entire length of the pores that no intermembrane gap is visible. Later on, during cell expansion, the plasmodesmata pore widens and the two membranes separate, leaving a cytosolic sleeve spanned by tethers whose presence correlates with the appearance of the intermembrane gap. Surprisingly, the post-cytokinesis plasmodesmata allow diffusion of macromolecules despite the apparent lack of an open cytoplasmic sleeve, forcing the reassessment of the mechanisms that control plant cell–cell communication.

Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear. Here, using a tunable system of chromosome mis-segregation, we show that mitotic errors trigger nuclear deformation, nuclear softening, and lamin and heterochromatin alterations, leading to rapid p53/p21 activation upon mitotic exit in response to changes in nuclear mechanics. We identify mTORC2 and ATR as nuclear deformation sensors upstream of p53/p21 activation. While triggering mitotic arrest, the chromosome mis-segregation-induced alterations of nuclear envelope mechanics provide a fitness advantage for aneuploid cells by promoting nuclear deformation resilience and enhancing pro-invasive capabilities. Collectively, this work identifies a nuclear mechanical checkpoint triggered by altered chromatin organization that probably plays a critical role in cellular transformation and cancer progression. Hervé, Scelfo et al. show that chromosome mis-segregation induces mTORC2- and ATR-mediated p53 activation through a mechanosensitive checkpoint at the nuclear envelope triggered by altered heterochromatin content and increased nuclear membrane tension.

We present CCD phase-binned light curves at 490 nm for 97 Cepheid variable stars in the bar of the LMC. The photometry was obtained as part of the French EROS project and has excellent phase coverage, permitting accurate decomposition into Fourier components. We identify as `sinusoidal' or s-Cepheids those stars with periods less than 5.5 d and small second-harmonic components. These stars comprise \\(\\sim\\)30% of our sample and most form a sequence \\(\\sim\\)1 mag brighter than the LMC classical Cepheids in the period-luminosity diagram. They are also generally bluer and have lower-amplitude light curves. We infer that the s-Cepheids are first-overtone pulsators because, when their periods are converted to expected fundamental-mode values, they obey a common period-luminosity-colour relation with classical Cepheids. This also confirms the reality of the colour term in the Cepheid period-luminosity-colour relation. Further, the blue edge of the classical Cepheid instability strip agrees well with the theoretical calculations for the fundamental mode made by Chiosi et al. (1993) for the Hertzsprung-Russell and period-luminosity diagrams, but we find that our observed s-Cepheids are \\(>0.2\\) mag brighter and bluer than the Chiosi et al.\\ predictions for the first-overtone. We identify a number of features in plots of our stars' Fourier-component amplitude ratios and phase differences. These features have been identified with resonances between different pulsation modes. In the LMC we find these features seem to occur at periods very similar to Galactic ones for classical Cepheids, but at different periods for s-Cepheids. We discover a double-mode Cepheid in the LMC, for which \\(P({\\rm first overtone})/P({\\rm fundamental}) = 0.710 \\pm 0.001\\), very similar to observed ratios for Galactic double-mode Cepheids.

Recent HST determinations of the expansion's rate of the Universe (the Hubble constant, H_0) assumed that the Cepheid Period-Luminosity relation at V and I are independent of metallicity (Freedman, et al., 1996, Saha et al., 1996, Tanvir et al., 1995). The three groups obtain different vales for H_0. We note that most of this discrepancy stems from the asumption (by both groups) that the Period-Luminosity relation is independent of metallicity. We come to this conclusion as a result of our study of the Period-Luminosity relation of 481 Cepheids with 3 millions two colour measurements in the Large Magellanic Cloud and the Small Magellanic Cloud obtained as a by-product of the EROS microlensing survey. We find that the derived interstellar absorption corrections are particularly sensitive to the metallicity and when our result is applied to recent estimates based on HST Cepheids observations it makes the low-H_0 values higher and the high-H_0 value lower, bringing those discrepant estimates into agrement around \\(H_0 \\approx 70 km/s Mpc^{-1}\\).

This is an investigation of the period-luminosity relation of classical Cepheids in samples of different metallicity. It is based on 481 Cepheids in the Large and Small Magellanic Clouds from the blue and red filter CCD observations (most similar to V_J & R_J) of the French EROS microlensing project. The data-set is complete and provides an excellent basis for a differential analysis between LMC and SMC. In comparison to previous studies of effects on the PL-relation, the EROS data-set offers extremely well-sampled light curves and well-filled instability strips. This allows reliable separation of Cepheids pulsating in the fundamental and the first overtone mode and derivation of differential reddening. Our main result concerns the determination of distances to galaxies which are inferred by using the LMC as a base and using two color photometry to establish the amount of reddening. We find a zero-point offset between SMC and LMC which amounts to a difference between inferred and true distance modulus of 0.14 \\pm 0.06 mag in the VI_c system. The offset is exactly the same in both sets of PL-relations - of the fundamental and of the first overtone mode Cepheids. No effect is seen on the slopes of the PL-relations, although the fundamental and the first overtone mode Cepheids have different PL slopes. We attribute the color and the zero-point offset to the difference in metallicity between the SMC and LMC Cepheids. A metallicity effect of that small magnitude still has important consequencies for the inferred Cepheid distances and the determination of H_0. When applied to recent estimates based on HST Cepheid observations, our metallicity dependence makes the low-H_0 values (Sandage et al. 1994) higher and the high-H_0 values (Freedman et al. 1994b) lower, thus bringing those

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.Gly1961Glu). We optimized ABCA4 base editing in human models, including retinal organoids, induced pluripotent stem cell-derived retinal pigment epithelial (RPE) cells, as well as adult human retinal explants and RPE/choroid explants in vitro. The resulting gene therapy vectors achieved high levels of gene correction in mutation-carrying mice and in female nonhuman primates, with average editing of 75% of cones and 87% of RPE cells in vivo, which has the potential to translate to a clinical benefit. No off-target editing was detectable in human retinal explants and RPE/choroid explants. The high editing rates in primates show promise for efficient gene editing in other ocular diseases that are targetable by base editing. A base-editing approach optimized to target the retina shows high editing rates in a mouse model of Stargardt disease, as well as in nonhuman primates and ex vivo human retinal explants, paving the way for potential clinical applications.

The Cluster spacecraft were favorably positioned on the nightside near the equatorial plasmapause of Earth at L ∼ 4.3 on 30 March 2002 to observe electromagnetic ion cyclotron (EMIC) rising tone emissions in association with Pc1 waves at 1.5 Hz. The EMIC rising tone emissions were found to be left‐hand, circularly polarized, dispersive, and propagating away from the equator. Their burstiness and dispersion of ∼30s/Hz rising out of the 1.5 Hz Pc1 waves are consistent with their identification as EMIC triggered chorus emissions, the first to be reported through in situ observations near the plasmapause. Along with the expected H+ ring current ions seen at higher energies (>300 eV), lower energy ions (300 eV and less) were observed during the most intense EMIC triggered emission events. Nonlinear wave‐particle interactions via cyclotron resonance between the ∼2–10 keV H+ ions with temperature anisotropy and the linearly‐amplified Pc1 waves are suggested as a possible generation mechanism for the EMIC triggered emissions.