Water level fluctuations are an inherent feature regulating the ecological structures and functions of lakes. It is vital to understand the effects of water level fluctuations on bacterial communities and metabolic characteristics in freshwater lakes in a changing world. However, information on the microbial community structure and functional properties in permanently and seasonally flooded areas are lacking. Poyang Lake is a typical seasonal lake linked to the Yangtze River and is significantly affected by water level fluctuations. Bottom water was collected from 12 sampling sites: seven inundated for the whole year (inundated areas) and five drained during the dry season (emerged areas). High-throughput 16S rRNA gene sequencing was used to identify the bacterial communities. The results showed that the taxonomic structure and potential functions of the bacterial communities were significantly different between the inundated and emerged areas. Cyanobacteria was dominant in both areas, but the relative abundance of Cyanobacteria was much higher in the emerged areas than in the inundated areas. Bacterial communities were taxonomically sensitive in the inundated areas and functionally sensitive in the emerged areas. Nitrogen, phosphorus, and dissolved organic carbon concentrations and their ratios, as well as dissolved oxygen, played important roles in promoting the bacterial taxonomic and functional compositional patterns in both areas. According to the metabolic predictions based on 16S rRNA gene sequences, the relative abundance of functional genes related to assimilatory nitrate reduction in the emerged areas was higher than in the inundated areas, and the relative abundance of functional genes related to dissimilatory nitrate reduction in the inundated areas was higher. These differences might have been caused by the nitrogen differences between the permanently and seasonally flooded areas caused by intra-annual water level fluctuations. The relative abundance of functional genes associated with denitrification was not significantly different in the inundated and emerged areas. This study improved our knowledge of bacterial community structure and nitrogen metabolic processes in permanently and seasonally flooded areas caused by water level fluctuations in a seasonal lake.

Bone metastases remain a serious health concern because of limited therapeutic options. Here, we report that crosstalk between ROR1-HER3 and the Hippo-YAP pathway promotes breast cancer bone metastasis in a long noncoding RNA-dependent fashion. Mechanistically, the orphan receptor tyrosine kinase ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307, following neuregulin stimulation, independently of other ErbB family members. p-HER3 Tyr1307 recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59. This methylation leads to MST1 inactivation and activation of YAP target genes in tumour cells, which elicits osteoclast differentiation and bone metastasis. Furthermore, increased ROR1, p-HER3 Tyr1307 and MAYA levels correlate with tumour metastasis and unfavourable outcomes. Our data provide insights into the mechanistic regulation and linkage of the ROR1-HER3 and Hippo-YAP pathway in a cancer-specific context, and also imply valuable therapeutic targets for bone metastasis and possible therapy-resistant tumours.

Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a plac-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. Several exopolysaccharide genes and motility genes were induced and downregulated, respectively, in in vivo PAO1 and the in vivo ΔwspF mutant compared to the in vivo plac-yhjH-containing strain. Elevation of c-di-GMP levels in P. aeruginosa began as early as 2 h postinfection. The ΔwspF mutant was less susceptible to host clearance than the plac-yhjH-containing strain and could suppress host immune responses. The type III secretion system (T3SS) was induced in in vivo PAO1 compared to in vitro biofilm bacteria. A ΔwspF mutant with a defective T3SS was more susceptible to host clearance than a ΔwspF mutant with a functional T3SS. Our study suggests that elevated intracellular c-di-GMP levels and T3SS activity in P. aeruginosa are necessary for establishment of infection and modulation of host immune responses in mouse cornea.