In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since glutathione cannot be reduced in the ER, maintenance of the ER GSH redox state and levels likely depend on ER GSH import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor GSH import into the ER of yeast cells. We found that GSH enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport. Increased ER GSH import triggers H2O2-dependent Bip oxidation through Ero1 reductive activation, which inhibits GSH import in a negative regulatory loop. During ER stress, transport is activated by UPR-dependent Ero1 induction and cytosolic GSH levels increase. Thus, the ER redox poise is tuned by reciprocal control of GSH import and Ero1 activation. The ER protein-conducting channel is thus permeable to small molecules, provided the driving force of a concentration gradient.

The distribution of cyanomyoviruses was estimated using a quantitative PCR (qPCR) approach that targeted the g20 gene as a proxy for phage. Samples were collected spatially during a > 3000 km transect through the Sargasso Sea and temporally during a gyre-constrained phytoplankton bloom within the southern Pacific Ocean. Cyanomyovirus abundances were lower in the Sargasso Sea than in the southern Pacific Ocean, ranging from 2.75 × 10(3) to 5.15 × 10(4) mL(-1) and correlating with the abundance of their potential hosts (Prochlorococcus and Synechococcus). Cyanomyovirus abundance in the southern Pacific Ocean (east of New Zealand) followed Synechococcus host populations in the system: this included a decrease in g20 gene copies (from 4.3 × 10(5) to 9.6 × 10(3) mL(-1) ) following the demise of a Synechococcus bloom. When compared with direct counts of viruses, observations suggest that the cyanomyoviruses comprised 0.5 to >25% of the total virus community. We estimated daily lysis rates of 0.2-46% of the standing stock of Synechococcus in the Pacific Ocean compared with c. < 1.0% in the Sargasso Sea. In total, our observations confirm this family of viruses is abundant in marine systems and that they are an important source of cyanobacterial mortality.

Background Diabetic foot ulcers (DFUs) account for the majority of all limb amputations and hospitalizations due to diabetes complications. With 30 million cases of diabetes in the USA and 500,000 new diagnoses each year, DFUs are a growing health problem. Diabetes patients with limb amputations have high postoperative mortality, a high rate of secondary amputation, prolonged inpatient hospital stays, and a high incidence of re-hospitalization. DFU-associated amputations constitute a significant burden on healthcare resources that cost more than 10 billion dollars per year. Currently, there is no way to identify wounds that will heal versus those that will become severely infected and require amputation. Main body Accurate identification of causative pathogens in diabetic foot ulcers is a critical component of effective treatment. Compared to traditional culture-based methods, advanced sequencing technologies provide more comprehensive and unbiased profiling on wound microbiome with a higher taxonomic resolution, as well as functional annotation such as virulence and antibiotic resistance. In this review, we summarize the latest developments in defining the microbiology of diabetic foot ulcers that have been unveiled by sequencing technologies and discuss both the future promises and current limitations of these approaches. In particular, we highlight the temporal patterns and system dynamics in the diabetic foot microbiome monitored and measured during wound progression and medical intervention, and explore the feasibility of molecular diagnostics in clinics. Conclusion Molecular tests conducted during weekly office visits to clean and examine DFUs would allow clinicians to offer personalized treatment and antibiotic therapy. Personalized wound management could reduce healthcare costs, improve quality of life for patients, and recoup lost productivity that is important not only to the patient, but also to healthcare payers and providers. These efforts could also improve antibiotic stewardship and control the rise of “superbugs” vital to global health.

Addressing the mechanisms controlling GSH traffic in and out of the ER/periplasm and its recycling will help address GSH function in secretion. In addition, as thioredoxin reductase was recently implicated in ER oxidative protein folding, the relative contribution of each of these two reducing pathways should now be addressed. Antioxid. Redox Signal. 27, 1178-1199.