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The relatively quiet mutational landscape of rhabdomyosarcoma (RMS) suggests that epigenetic deregulation could be central to oncogenesis and tumour aggressiveness. Histone variants have long been recognised as important epigenetic regulators of gene expression. However, the role of histone variants in RMS has not been studied hitherto. In this study, we show that histone variant H3.3 is overexpressed in alveolar rhabdomyosarcoma (ARMS), an aggressive subtype of RMS. Functionally, knockdown of H3F3A, which encodes for H3.3, significantly impairs the ability of ARMS cells to undertake migration and invasion and reduces Rho activation. In addition, a striking reduction in metastatic tumour burden and improved survival is apparent in vivo. Using RNA-sequencing and ChIP-sequencing analyses, we identified Melanoma Cell Adhesion Molecule (MCAM/CD146) as a direct downstream target of H3.3. Loss of H3.3 resulted in a reduction in the presence of active marks, and an increase in the occupancy of H1 at the MCAM promoter. Cell migration and invasion were rescued in H3F3A-depleted cells through MCAM overexpression. Moreover, we identified G9a, a lysine methyltransferase encoded by EHMT2, as an upstream regulator of H3F3A. Therefore, this study identifies a novel H3.3 dependent axis involved in ARMS metastasis. These findings establish the potential of MCAM as a therapeutic target for high-risk ARMS patients. This article is protected by copyright. All rights reserved.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of different types of topical immunosuppressive treatments for eczema. To generate rankings of the available topical immunosuppressive treatments for eczema, according to their efficacy and safety.

Organic–inorganic heterostructures are an emerging topic that is very interesting for optoelectronics. Here, non-conventional p–n junctions are investigated using organic rubrene single crystal and 2D MoS2 as the p- and n-type semiconducting materials, respectively. The current-rectifying behavior is clearly observed in the junction device. The rectification ratio can be electrically tuned by the gate voltage due to the 2D nature of the heterostructure. The devices also show good photoresponse properties with a photoresponsivity of ≈500 mA W−1 and a fast response time. These findings suggest a new route to facilitate the design of nanoelectronic and optoelectronic devices based on layered inorganics and organics.

Aim Previous work on the tidepool copepod Tigriopus californicus revealed a curious case of incipient speciation at the southern end of the species' range in Baja California, Mexico. The present study expands on the geography of this pattern and tests for congruence between reproductive and phylogenetic patterns. Location The Pacific coast of North America, from central Baja California to south-eastern Alaska (27–57° N), including the full range of T. californicus. Methods Primary techniques included mating experiments (> 4000 crosses), phylogeny reconstruction (mitochondrial cytochrome c oxidase subunit I) and screening of single nucleotide polymorphisms (SNPs, 42 loci). Analyses used > 8000 copepods for the mating experiments, 86 copepods for the phylogeny and 41 copepods for the SNP assays. Phylogenies were constructed using Bayesian, maximum likelihood and maximum parsimony methods. Results Populations were found to fall into three reproductive groups: northern and southern groups that were reproductively isolated from each other, and an intermediate group that could serve as a conduit for gene flow. The northern and intermediate populations fell into one clade while all southern populations fell into a second clade. These two clades are now separated by less than 12 km at latitude 29.35° N. Nuclear SNP data for a subset of locations confirmed striking divergence between populations on either side of this boundary. The second (southern) clade was further subdivided into two clades separated by the lagoon region of Guerrero Negro (latitude 28° N). Main conclusions Reproductive assays and molecular data (both mitochondrial and nuclear) reveal a sharp break at 29.35° N, a region with no obvious barriers to dispersal, with no evidence for mixing across this narrow transition zone. Results also showed a milder break at the Guerrero Negro Lagoon (28° N), a location where breaks have been reported for other taxa.

Fragmentation and propagule formation are alternative reproductive strategies found in both plants and animals, with the latter generally providing greater dispersal capability. When both strategies occur, life history theory predicts that resources should be divided between the two. On coral reefs, both strategies are exhibited by branching corals and sponges, which are broken-up after storm events and rapidly recolonize. In this study, we compared two congeneric Caribbean reef sponges, Callyspongia armigera, which is branched and easily fragmented, and C. vaginalis, which is not, to test whether there is a tradeoff in growth and propagule formation for C. armigera relative to C. vaginalis. Both species were equally abundant on coral reefs off Key Largo, Florida (10.1 3.7 vs 11.9 3.0 per 100 m 2 , respectively), suggesting that they are equally successful relative to two other non-fragmenting congeneric species (C. fallax and C. plicifera) that are much less common. Th e number of substratum attachment points per sponge was signifi cantly higher for C. armigera compared to C. vaginalis (2.31 1.47 vs 1.03 0.18 sponge –1 ), providing further evidence of the reliance of C. armigera on fragmentation, and of C. vaginalis on recruitment from larval settlement and subsequent growth. Growth rates in predator-exclusion experiments were ~4-fold higher for C. armigera compared to C. vaginalis (0.36 0.31 vs 0.08 0.11 % initial mass day –1 ), but C. armigera produced ~13-fold fewer propagules than C. vaginalis (0.04 0.22 vs 0.53 1.08 % tissue area). Our results support a tradeoff between growth and propagule output for C. armigera relative to C. vaginalis, suggesting that these closely related sponge species took diff erent evolutionary trajectories in reconciling their resource constraints.

Molybdenum disulfide (MoS2) has attracted vast interest in the fields of electronic, optoelectronic, and valleytronic applications due to its unique properties. Because of its low dimensionality, MoS2 is susceptible to oxygen absorption in ambient environments, which can alter its electrical and optical properties. Here, a new method to introduce oxygen chemisorption in ultrathin MoS2 by controlled oxygen plasma treatment is presented. Using Raman spectroscopy, a red shift in the frequency of E12g mode with increasing oxygen chemisorption is found, whereas, the frequency of A1g mode is fixed. Interestingly, the absorption peak in the photoluminescence spectra red shifts, indicating an optical band gap reduction upon oxygen chemisorption. The behaviors of these different shifts are reproduced and elucidated by density functional theory calculations. It is found that the red shift of the E12g Raman peak is caused by a softening of in-plane Mo-S force constants, while the red shift in the photoluminescence peak is due to a reduction of the electronic band gap in oxygen-chemisorbed MoS2. The results shine light on the fundamental understanding of chemical interactions between oxygen and MoS2 and provide an alternative way to achieve band gap engineering in MoS2.