Amphiregulin Regulates Melanocytic Senescence

Oncogene-induced senescence (OIS) is a decisive process to suppress tumor development, but the molecular details of OIS are still under investigation. Using an established OIS model of primary melanocytes transduced with BRAF V600E and compared to control cells, amphiregulin (AREG) was shown to be induced. In addition, AREG expression was observed in nevi, which by definition, are senescent cell clusters, compared to melanocytes. Interestingly, treatment of melanocytes with recombinant AREG did induce senescence. This led to the assumption that extracellular AREG has an important function in this process. Inhibition of the epidermal growth factor receptor (EGFR) using Gefitinib identified AREG as one of EGFR ligands responsible for senescence. Furthermore, depletion of AREG expression in senescent BRAF V600E melanocytes resulted in a significant reduction of senescent melanocytes. This study reveals AREG as an essential molecular component of signaling pathways leading to senescence in melanocytes.

ESTIMATED RELATIONS BETWEEN THE MAIN THERMOSPHERIC NEUTRAL COMPONENTS AT IONOSPHERIC F1-LAYER HEIGHTSABOVE IRKUTSK IN 2014–2017

We have estimated seasonal variations in the main thermospheric gas components [O]/[N₂] and [O₂]/[O] for the period 2014–2017. We have used the well-known authoring technique and electron density measurements made with the Irkutsk digisonde (52° N, 104° E) at ionospheric F1-layer heights under different geomagnetic activity conditions. We have found that at these heights during geomagnetic disturbances in all seasons the molecular component of the neutral composition of the thermosphere increases and the atomic component decreases. In comparison with 2014, [O₂]/[O] values increased by 2017 under quiet and disturbed geomagnetic conditions: up to 30 % and 20 % in summer and spring respectively; up to 10 % in winter and autumn. The [O]/[N₂] ratio decreased by an average of 15 % by 2017. The assumption has been confirmed that in summer under quiet geomagnetic conditions the relative molecular oxygen content [O₂]/[O] increases with decreasing solar activity.

ESTIMATED RELATIONS BETWEEN THE MAIN THERMOSPHERIC NEUTRAL COMPONENTS AT IONOSPHERIC F1-LAYER HEIGHTSABOVE IRKUTSK IN 2014–2017

We have estimated seasonal variations in the main thermospheric gas components [O]/[N₂] and [O₂]/[O] for the period 2014–2017. We have used the well-known authoring technique and electron density measurements made with the Irkutsk digisonde (52° N, 104° E) at ionospheric F1-layer heights under different geomagnetic activity conditions. We have found that at these heights during geomagnetic disturbances in all seasons the molecular component of the neutral composition of the thermosphere increases and the atomic component decreases. In comparison with 2014, [O₂]/[O] values increased by 2017 under quiet and disturbed geomagnetic conditions: up to 30 % and 20 % in summer and spring respectively; up to 10 % in winter and autumn. The [O]/[N₂] ratio decreased by an average of 15 % by 2017. The assumption has been confirmed that in summer under quiet geomagnetic conditions the relative molecular oxygen content [O₂]/[O] increases with decreasing solar activity.

Inhibition mechanisms of AcrF9, AcrF8, and AcrF6 against type I-F CRISPR–Cas complex revealed by cryo-EM

Prokaryotes and viruses have fought a long battle against each other. Prokaryotes use CRISPR–Cas-mediated adaptive immunity, while conversely, viruses evolve multiple anti-CRISPR (Acr) proteins to defeat these CRISPR–Cas systems. The type I-F CRISPR–Cas system in Pseudomonas aeruginosa requires the crRNA-guided surveillance complex (Csy complex) to recognize the invading DNA. Although some Acr proteins against the Csy complex have been reported, other relevant Acr proteins still need studies to understand their mechanisms. Here, we obtain three structures of previously unresolved Acr proteins (AcrF9, AcrF8, and AcrF6) bound to the Csy complex using electron cryo-microscopy (cryo-EM), with resolution at 2.57 Å, 3.42 Å, and 3.15 Å, respectively. The 2.57-Å structure reveals fine details for each molecular component within the Csy complex as well as the direct and water-mediated interactions between proteins and CRISPR RNA (crRNA). Our structures also show unambiguously how these Acr proteins bind differently to the Csy complex. AcrF9 binds to key DNA-binding sites on the Csy spiral backbone. AcrF6 binds at the junction between Cas7.6f and Cas8f, which is critical for DNA duplex splitting. AcrF8 binds to a distinct position on the Csy spiral backbone and forms interactions with crRNA, which has not been seen in other Acr proteins against the Csy complex. Our structure-guided mutagenesis and biochemistry experiments further support the anti-CRISPR mechanisms of these Acr proteins. Our findings support the convergent consequence of inhibiting degradation of invading DNA by these Acr proteins, albeit with different modes of interactions with the type I-F CRISPR–Cas system.

Cloud formation in the atomic and molecular phase: H I self absorption (HISA) towards a giant molecular filament

Molecular clouds form from the atomic phase of the interstellar medium. However, characterizing the transition between the atomic and the molecular interstellar medium (ISM) is a complex observational task. Here we address cloud formation processes by combining H I self absorption (HISA) with molecular line data. Column density probability density functions (N-PDFs) are a common tool for examining molecular clouds. One scenario proposed by numerical simulations is that the N-PDF evolves from a log-normal shape at early times to a power-law-like shape at later times. To date, investigations of N-PDFs have been mostly limited to the molecular component of the cloud. In this paper, we study the cold atomic component of the giant molecular filament GMF38.1-32.4a (GMF38a, distance = 3.4 kpc, length ~ 230 pc), calculate its N-PDFs, and study its kinematics. We identify an extended HISA feature, which is partly correlated with the 13CO emission. The peak velocities of the HISA and 13CO observations agree well on the eastern side of the filament, whereas a velocity offset of approximately 4 km s−1 is found on the western side. The sonic Mach number we derive from the linewidth measurements shows that a large fraction of the HISA, which is ascribed to the cold neutral medium (CNM), is at subsonic and transonic velocities. The column density of the CNM part is on the order of 1020 to 1021 cm−2. The column density of molecular hydrogen, traced by 13CO, is an order of magnitude higher. The N-PDFs from HISA (CNM), H I emission (the warm and cold neutral medium), and 13CO (molecular component) are well described by log-normal functions, which is in agreement with turbulent motions being the main driver of cloud dynamics. The N-PDF of the molecular component also shows a power law in the high column-density region, indicating self-gravity. We suggest that we are witnessing two different evolutionary stages within the filament. The eastern subregion seems to be forming a molecular cloud out of the atomic gas, whereas the western subregion already shows high column density peaks, active star formation, and evidence of related feedback processes.

Theory of hadronic molecules applied to the XYZ states

In recent years data have been accumulated at various experiments about states in the heavy quarkonium mass range that seem to be inconsistent with the most simple variants of the quark model. In this contribution it is demonstrated that most of those data are consistent with a dominant molecular nature of those states. It is also discussed which kind of observables are sensitive to the molecular component and which are not.

Variation in opsin transcript expression explains intraretinal differences in spectral sensitivity of the northern anchovy

Vertebrate retinal photoreceptors house visual pigments that absorb light to begin the process of vision. The light absorbed by a visual pigment depends on its two molecular components: protein (opsin) and chromophore (a vitamin A derivative). Although an increasing number of studies show intraretinal variability in visual pigment content, it is only for two mammals (human and mouse) and two birds (chicken and pigeon) that such variability has been demonstrated to underlie differences in spectral sensitivity of the animal. Here, we show that the spectral sensitivity of the northern anchovy varies with retinal quadrant and that this variability can be explained by differences in the expression of opsin transcripts. Retinal (vitamin A1) was the only chromophore detected in the retina, ruling out this molecular component as a source of variation in spectral sensitivity. Chromatic adaptation experiments further showed that the dorsal retina had the capacity to mediate color vision. Together with published results for the ventral retina, this study is the first to demonstrate that intraretinal opsin variability in a fish drives corresponding variation in the animal’s spectral sensitivity.