The Pseudomonas aeruginosa phosphate transport protein PstS plays a phosphate-independent role in biofilm formation.

Pseudomonas aeruginosa (PA) is a primary cause of nosocomial infections. A key element in PA pathogenicity is its ability to form biofilms that withstand eradication by antibiotics and the immune system. Biofilm formation is controlled by phosphate signaling and here we provide evidence that PstS, a subunit of the PA Pst phosphate transporter, has a surprising role in this process. Using X-ray crystallography, we characterized the unique underpinnings of PstS phosphate binding and identified an unusual 15-residue N' loop extension. Structure-based experiments showed that PstS-mediated phosphate uptake and biofilm formation are in fact two distinct functions. Specifically, a point mutation that abrogated phosphate binding did not eliminate biofilm formation; conversely, truncation of the N' loop diminished the ability of PA to form biofilms but had no effect on phosphate binding and uptake. This places PstS at a junction that separately controls phosphate sensing and uptake and the ultrastructure organization of bacteria.

"We have knowledge that is unique": Patient activism and the promotion of trans-inclusive primary care.

Despite growing visibility of the trans population in Israel, there has been limited research on trans healthcare in a local context, particularly in the field of primary care medicine. Primary care encompasses services provided in locally distributed clinics and has a crucial role in providing both preventive and specialized healthcare. The aim of this study is to outline barriers to trans-inclusive primary care and measures employed by the trans community to overcome them. Biopower and counter-conduct are used as analytical frameworks to examine the trans-exclusionary features of the Israeli healthcare system and steps taken to resist it. To examine these issues, 19 medical care professionals and 20 trans people and activists were interviewed, and a variety of relevant texts were analyzed. Our results indicate trans-exclusionary features in primary healthcare, such as ambiguity regarding trans-inclusive services offered, sex-specific treatments, and lack of medical training programs dedicated to the trans population. To overcome these difficulties, the Israeli trans community has accumulated communal experiential knowledge and transferred it to physicians and policymakers in a localized and informal manner. We argue that by using informal practices, the trans community can provide support and information to its own members as well as operate alongside power systems, albeit in a slow and lengthy manner. More generally, the findings of this study highlight howf patient activism is employed by marginalized populations, who face not only health disparities, but institutional discrimination as well.

The role of DNA demethylation in liver to pancreas transdifferentiation.

BACKGROUND: Insulin producing cells generated by liver cell transdifferentiation, could serve as an attractive source for regenerative medicine. The present study assesses the relationship between DNA methylation pTFs induced liver to pancreas transdifferentiation. RESULTS: The transdifferentiation process is associated with DNA demethylation, mainly at gene regulatory sites, and with increased expression of these genes. Active inhibition of DNA methylation promotes the pancreatic transcription factor-induced transdifferentiation process, supporting a causal role for DNA demethylation in this process. CONCLUSIONS: Transdifferentiation is associated with global DNA hypomethylation, and with increased expression of specific demethylated genes. A combination of epigenetic modulators may be used to increase chromatin accessibility of the pancreatic transcription factors, thus promoting the efficiency of the developmental process.

The effect of pstS and phoB on quorum sensing and swarming motility in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause a wide range of infections and inflammations in a variety of hosts, such as chronic biofilm associated lung infections in Cystic Fibrosis patients. Phosphate, an essential nutrient, has been recognized as an important signal that affects virulence in P. aeruginosa. In the current study we examined the connection between phosphate regulation and surface motility in P. aeruginosa. We focused on two important genes, pstS, which is involved in phosphate uptake, and phoB, a central regulator that responds to phosphate starvation. We found that a mutant lacking pstS is constantly starved for phosphate and has a hyper swarming phenotype. Phosphate starvation also induced swarming in the wild type. The phoB mutant, on the other hand, did not express phosphate starvation even when phosphate was limited and showed no swarming. A double mutant lacking both genes (pstS and phoB) showed a similar phenotype to the phoB mutant (i.e. no swarming). This highlights the role of phoB in controlling swarming motility under phosphate-depleted conditions. Finally, we were able to demonstrate that PhoB controls swarming by up-regulating the Rhl quorum sensing system in P. aeruginosa, which resulted in hyper production of rhamonlipids: biosurfactants that are known to induce swarming motility.