Objective: Dysbiosis of gastric microbiota such as Helicobacter pylori plays a significant role in pathogenesis and progression of gastric cancer. Our aim was to evaluate the composition and functional effects of gastric microbiota in superficial gastritis (SG) and advanced gastric adenocarcinoma (GC).Methods: We carried out shotgun metagenomic sequencing on gastric wash samples from 6 patients with GC and 5 patients with SG. The taxonomic composition was profiled using MetaPhlAn2 and functional gene pathway was profiled using HUMAnN2. Differences in microbial composition and pathways between the two patient groups were assessed via LEfSe.Results: The gastric microbiota in GC patients was characterized by reduced species richness, enrichment of 13 bacterial taxa and depletion of 31 taxa (q < 0.05). The most representative taxa which were abundant in GC corresponded to the commensals or opportunistic pathogens that usually colonize the oral cavity, including genera Neisseria, Alloprevotella, and Aggregatibacter, species Streptococcus_mitis_oralis_pneumoniae and strain Porphyromonas_endodontalis.t_GCF_000174815. Each of the three GC-associated genera could separate GC from SG completely. In particular, Sphingobium yanoikuyae, a bacterium capable of degrading carcinogenic compounds, was depleted in GC. Functionally, pathways associated with the biosynthesis of lipopolysaccharide (LPS) and L-arginine were enriched in GC, whereas pathways involved in the fermentation of short chain fatty acids (SCFAs) and branched amino acid metabolism were more abundant in SG.Conclusions: Our results present new alterations in the gastric microbiome in patients with GC from a whole-genome perspective, suggesting that microbiome composition and function can be used for prognosis and diagnosis of GC.

The maternal-to-zygotic transition (MZT) marks the period when the embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at the 2-cell stage in mice. We investigated the function of the maternally inherited factor Stella (encoded by Dppa3) using single-cell/embryo approaches. We show that loss of maternal Stella results in widespread transcriptional mis-regulation and a partial failure of MZT. Strikingly, activation of endogenous retroviruses (ERVs) is significantly impaired in Stella maternal/zygotic knockout embryos, which in turn leads to a failure to upregulate chimeric transcripts. Amongst ERVs, MuERV-L activation is particularly affected by the absence of Stella, and direct in vivo knockdown of MuERV-L impacts the developmental potential of the embryo. We propose that Stella is involved in ensuring activation of ERVs, which themselves play a potentially key role during early development, either directly or through influencing embryonic gene expression.DOI: http://dx.doi.org/10.7554/eLife.22345.001

The spreading and migration of cells on adhesive substrates is regulated by the counterbalance of contractile and protrusive forces. Non-muscle myosin IIA, an ubiquitously expressed contractile protein and enzyme, is implicated in the regulation of cell spreading and directional migration in response to various stimuli. Here we show that discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor activated by type I collagen, associates with the non-muscle myosin IIA heavy chain (NMHC-IIA) upon ligand stimulation. An association was also indicated by coimmunoprecipitation of NMHC-IIA with fulllength DDR1, but not with the truncated DDR1d-isoform lacking the kinase domain. DDR1 was important for assembly of NMHC-IIA into filaments on cells plated on collagen. DDR1 expression inhibited cell spreading over collagen but promoted cell migration. By contrast, blockade of non-muscle myosin II activity by blebbistatin enhanced cell spreading but inhibited migration over collagen. We propose that myosin and DDR1 impact cell spreading and migration by regulating adhesive contacts with collagen.