Context. The detection of mixed modes that are split by rotation in Kepler red giants has made it possible to probe the internal rotation profiles of these stars, which brings new constraints on the ...transport of angular momentum in stars. Rotation rates in the central regions of intermediate-mass core helium burning stars (secondary clump stars) have recently been measured. Aims. Our aim is to exploit the rotational splittings of mixed modes to estimate the amount of radial differential rotation in the interior of secondary clump stars using Kepler data in order to place constraints on angular momentum transport in intermediate-mass stars. Methods. We select a subsample of Kepler secondary clump stars with mixed modes that are clearly rotationally split. By applying a thorough statistical analysis, we show that the splittings of gravity-dominated modes (trapped in central regions) and of p-dominated modes (trapped in the envelope) can be measured. We then use these splittings to estimate the amount of differential rotation by using inversion techniques and by applying a simplified approach based on asymptotic theory. Results. We obtain evidence for a weak radial differential rotation for six of the seven targets that were selected, with the central regions rotating from 1.8 ± 0.3 to 3.2 ± 1.0 times faster than the envelope. The last target is found to be consistent with a solid-body rotation. Conclusions. This demonstrates that an efficient redistribution of angular momentum occurs after the end of the main sequence in the interior of intermediate-mass stars, either during the short-lived subgiant phase or once He-burning has started in the core. In either case, this should bring constraints on the angular momentum transport mechanisms that are at work.
Neurons are large and long lived, creating high needs for regulating protein turnover. Disturbances in proteostasis lead to aggregates and cellular stress. We characterized the behavior of the ...short-lived dendritic membrane proteins Nsg1 and Nsg2 to determine whether these proteins are degraded locally in dendrites or centrally in the soma. We discovered a spatial heterogeneity of endolysosomal compartments in dendrites. Early EEA1-positive and late Rab7-positive endosomes are found throughout dendrites, whereas the density of degradative LAMP1- and cathepsin (Cat) B/D-positive lysosomes decreases steeply past the proximal segment. Unlike in fibroblasts, we found that the majority of dendritic Rab7 late endosomes (LEs) do not contain LAMP1 and that a large proportion of LAMP1 compartments do not contain CatB/D. Second, Rab7 activity is required to mobilize distal predegradative LEs for transport to the soma and terminal degradation. We conclude that the majority of dendritic LAMP1 endosomes are not degradative lysosomes and that terminal degradation of dendritic cargos such as Nsg1, Nsg2, and DNER requires Rab7-dependent transport in LEs to somatic lysosomes.
We present the stellar kinematic maps of a large sample of galaxies from the integral-field spectroscopic survey CALIFA. The sample comprises 300 galaxies displaying a wide range of morphologies ...across the Hubble sequence, from ellipticals to late-type spirals. This dataset allows us to homogeneously extract stellar kinematics up to several effective radii. In this paper, we describe the level of completeness of this subset of galaxies withrespect to the full CALIFA sample, as well as the virtues and limitations of the kinematic extraction compared to other well-known integral-field surveys. In addition, we provide averaged integrated velocity dispersion radial profiles for different galaxy types, which are particularly useful to apply aperture corrections for single aperture measurements or poorly resolved stellar kinematics of high-redshift sources. The work presented in this paper sets the basis for the study of more general properties of galaxies that will be explored in subsequent papers of the survey.
Tumor-associated macrophages are major contributors to malignant progression and resistance to immunotherapy, but the mechanisms governing their differentiation from immature myeloid precursors ...remain incompletely understood. In this study, we demonstrate that exosomes secreted by human and mouse tumor-educated mesenchymal stem cells (MSCs) drive accelerated breast cancer progression by inducing differentiation of monocytic myeloid-derived suppressor cells into highly immunosuppressive M2-polarized macrophages at tumor beds. Mechanistically, MSC-derived exosomes but not exosomes from tumor cells contain TGF-β, C1q, and semaphorins, which promote myeloid tolerogenic activity by driving PD-L1 overexpression in both immature myelomonocytic precursors and committed CD206
macrophages and by inducing differentiation of MHC class II
macrophages with enhanced l-Arginase activity and IL-10 secretion at tumor beds. Accordingly, administration of tumor-associated murine MSC-derived exosomes accelerates tumor growth by dampening antitumor immunity, and macrophage depletion eliminates exosome-dependent differences in malignant progression. Our results unveil a new role for MSC-derived exosomes in the differentiation of myeloid-derived suppressor cells into macrophages, which governs malignant growth.
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses ...PD-L1 expression and limits tumor progression in ovarian cancer. CD274 (encoding PD-L1) is a direct target of BRD4-mediated gene transcription. In mouse models, treatment with the BET inhibitor JQ1 significantly reduced PD-L1 expression on tumor cells and tumor-associated dendritic cells and macrophages, which correlated with an increase in the activity of anti-tumor cytotoxic T cells. The BET inhibitor limited tumor progression in a cytotoxic T-cell-dependent manner. Together, these data demonstrate a small-molecule approach to block PD-L1 signaling. Given the fact that BET inhibitors have been proven to be safe with manageable reversible toxicity in clinical trials, our findings indicate that pharmacological BET inhibitors represent a treatment strategy for targeting PD-L1 expression.
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•BET inhibitors suppress PD-L1 expression in both immune cells and tumor cells•CD274 is a direct target gene of BRD4•BET inhibitors increase cytotoxic T cell activity to limit tumor progression in mice
Zhu et al. find that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian cancer in mice. CD274 (encoding PD-L1) is a direct target of BRD4-mediated gene transcription. Together, these data suggest a small-molecule approach to blocking PD-L1 signaling.
In this paper, the use of polymer additive manufacturing technology, also called 3D printing, for imparting texture to bond regions in adhesively bonded joints is explored. An improvement in the ...apparent shear strength values of adhesively bonded single lap joints is achieved by fusing structural reinforcements to the adherents through fused deposition modeling (FDM) additive technique. Towards that, computational models were first developed to simulate stress distribution along the overlap region of single lap shear joints, and four models that performed the best were chosen for physical testing. Pure adhesive (PA) joints were manufactured first, followed by the fabrication of 3D-printed adhesive (3D-PA) joints. Peak loads, shear stresses, and failure types were compared between these models. PA joints failed mainly adhesively, resulting in low peak loads and shear strength, whereas, 3D-PA joints registered higher average peak loads and shear strengths (increased by up to ≈832 %) with predominantly cohesive failure. 3D printed reinforcements appear to have imparted higher shear resistance against failure at the bond regions. Overall, using a combined computational and experimental approach, it is established that the 3D printed reinforcements have the potential to drastically improve the apparent shear strength of adhesively bonded single lap joints.
Computer-mediated communication (CMC) is pervasive in our lives, influencing social interaction including human courtship. To connect with potential partners via CMC, modern relationship-seekers must ...master faster and shorter methods of communicating self-disclosure and affect. Although CMC can lack crucial sensory information in this context, emojis may provide useful aid. Across two studies, we assessed attitudes toward and frequency of emoji use, and whether signaling affect via emoji use relates to more romantic and sexual opportunities. Our findings suggest that emoji use with potential partners is associated with maintaining connection beyond the first date, and more romantic and sexual interactions over the previous year. This research provides evidence that emojis convey important affective information to potential partners, and are potentially associated with more successful intimate connection. Implications for multiple theoretical models and methodologies are discussed.
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