The chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) controls cellular quiescence by hyperpolarizing the cell membrane during diapause in the crustacean Artemia

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (V-mem) and quiescence. We found that V-mem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas V-mem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high V-mem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and up-regulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and V-mem in the Artemia model

Using environmental DNA for detection of Batrachochytrium salamandrivorans in natural water

Rapid, early, and reliable detection of invasive pathogenic microorganisms is essential in order to either predict or delineate an outbreak, and monitor appropriate mitigation measures. The chytrid fungus Batrachochytrium salamandrivorans is expanding in Europe, and infection with this fungus may cause massive mortality in urodelans (salamanders and newts). In this study, we designed and validated species‐specific primers and a probe for detection of B. salamandrivorans in water. In a garden pond in close proximity to the B. salamandrivorans index site in the Netherlands, B. salamandrivorans‐infected newts had been detected in 2015 and have been monitored since. In 2016 and 2017, no B. salamandrivorans was detected at this site, but in 2018 B. salamandrivorans flared up in this isolated pond which allowed validation of the technique in situ. We here present the development of an environmental DNA technique that successfully detects B. salamandrivorans DNA in natural waterbodies even at low concentrations. This technique may be further validated to play a role in B. salamandrivorans range delineation and surveillance in both natural waterbodies and in captive collections

The impact of a deep-water plunging breaker on a wall with its bottom edge close to the mean water surface

The impact of a deep-water plunging breaker on a finite height two-dimensional structure with a vertical front face is studied experimentally. The structure is located at a fixed horizontal position relative to a wave maker and the structure’s bottom surface is located at a range of vertical positions close to the undisturbed water surface. Measurements of the water surface profile history and the pressure distribution on the front surface of the structure are performed. As the vertical position, (the axis is positive up and is the mean water level), of the structure’s bottom surface is varied from one experimental run to another, the water surface evolution during impact can be categorized into three classes of behaviour. In class I, with in a range of values near , where is the nominal wavelength of the breaker, the behaviour of the water surface is similar to the flip-through phenomena first described in studies with shallow water and a structure mounted on the sea bed. In the present work, it is found that the water surface between the front face of the structure and the wave crest is well fitted by arcs of circles with a decreasing radius and downward moving centre as the impact proceeds. A spatially and temporally localized high-pressure region was found on the impact surface of the structure and existing theory is used to explore the physics of this phenomenon. In class II, with in a range of values near the mean water level, the bottom of the structure exits and re-enters the water phase at least once during the impact process. These air–water transitions generate large-amplitude ripple packets that propagate to the wave crest and modify its behaviour significantly. At , all sensors submerged during the impact record a nearly in-phase high-frequency pressure oscillation indicating possible air entrainment. In class III, with in a range of values near , the bottom of the structure remains in air before the main crest hits the bottom corner of the structure. The subsequent free surface behaviour is strongly influenced by the instantaneous momentum of the local flow just before impact and the highest wall pressures of all experimental conditions are found

Deacetylation of p53 induces autophagy by suppressing Bmf expression

Interferon γ (IFN-γ)–induced cell death is mediated by the BH3-only domain protein, Bik, in a p53-independent manner. However, the effect of IFN-γ on p53 and how this affects autophagy have not been reported. The present study demonstrates that IFN-γ down-regulated expression of the BH3 domain-only protein, Bmf, in human and mouse airway epithelial cells in a p53-dependent manner. p53 also suppressed Bmf expression in response to other cell death–stimulating agents, including ultraviolet radiation and histone deacetylase inhibitors. IFN-γ did not affect Bmf messenger RNA half-life but increased nuclear p53 levels and the interaction of p53 with the Bmf promoter. IFN-γ–induced interaction of HDAC1 and p53 resulted in the deacetylation of p53 and suppression of Bmf expression independent of p53’s proline-rich domain. Suppression of Bmf facilitated IFN-γ–induced autophagy by reducing the interaction of Beclin-1 and Bcl-2. Furthermore, autophagy was prominent in cultured bmf−/− but not in bmf+/+ cells. Collectively, these observations show that deacetylation of p53 suppresses Bmf expression and facilitates autophagy

Willman 1 - a probable dwarf galaxy with an irregular kinematic distribution

We investigate the kinematic properties and stellar population of the Galactic satellite Willman 1 (Wil 1) by combining Keck/DEIMOS spectroscopy with KPNO mosaic camera imaging. Wil 1 is an ultra-low luminosity Milky Way companion. This object lies in a region of size-luminosity space (M_V ~ -2 mag, d ~ 38 kpc, r_half ~ 20 pc) also occupied by the Galactic satellites Bo\"otes II and Segue 1 and 2, but no other known old stellar system. We use kinematic and color-magnitude criteria to identify 45 stars as possible members of Wil 1. With a systemic velocity of v_helio = -12.8 +/- 1.0 km/s, Wil 1 stars have velocities similar to those of foreground Milky Way stars. Informed by Monte-Carlo simulations, we identify 5 of the 45 candidate member stars as likely foreground contaminants. We confirm a significant spread in the abundances of the likely Wil 1 red giant branch members ([Fe/H] = -1.73 +/- 0.12 and -2.65 +/- 0.12, [Ca/Fe] = -0.4 +/- 0.18 and +0.13 +/- 0.28). This spread supports the scenario that Wil 1 is an ultra-low luminosity dwarf galaxy rather than a star cluster. Wil 1's innermost stars move with radial velocities offset by 8 km/s from its outer stars and have a velocity dispersion consistent with 0 km/s, suggesting that Wil 1 may not be in dynamical equilibrium. The combination of the foreground contamination and unusual kinematic distribution make it difficult to robustly determine the dark matter mass of Wil 1. As a result, X-ray or gamma-ray observations of Wil 1 that attempt to constrain models of particle dark matter using an equilibrium mass model are strongly affected by the systematics in the observations presented here. We conclude that, despite the unusual features in the Wil 1 kinematic distribution, evidence indicates that this object is, or at least once was, a dwarf galaxy.Comment: AJ accepted version. The primary improvements are a detailed investigation of the membership probability (Section 3.4 and new Figures 6, 7 and 8) and the revised spectroscopic [Fe/H] and [Ca/Fe] measurements of the two brightest member stars. Conclusions are unchanged from the submitted versio

Emergent Phenomena Induced by Spin-Orbit Coupling at Surfaces and Interfaces

Spin-orbit coupling (SOC) describes the relativistic interaction between the spin and momentum degrees of freedom of electrons, and is central to the rich phenomena observed in condensed matter systems. In recent years, new phases of matter have emerged from the interplay between SOC and low dimensionality, such as chiral spin textures and spin-polarized surface and interface states. These low-dimensional SOC-based realizations are typically robust and can be exploited at room temperature. Here we discuss SOC as a means of producing such fundamentally new physical phenomena in thin films and heterostructures. We put into context the technological promise of these material classes for developing spin-based device applications at room temperature

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution