are urgently needed. Here we submitted the marine algae Phaeodactylum tricornutum to a 4-day dark stress, a condition increasing by 2.3-fold the total lipid cell quotas, and studied the cellular mechanisms leading to lipid accumulation using a combination of physiological, proteomic (iTRAQ) and genomic (qRT-PCR) approaches. Our results show that the expression of proteins in the biochemical pathways of glycolysis and the synthesis of fatty acids were induced in the dark, potentially using excess carbon and nitrogen produced from protein breakdown. Treatment of algae in the dark, which increased algal lipid cell quotas at low cost, combined with optimal growth treatment could help optimizing biodiesel production.As the world demand of fossil fuels increases and the greenhouse gas carbon dioxide levels continues to rise, the development of cost-effective biofuels is of high importance and should be a priority 1 . Microalgae are considered as one of the most promising biodiesel sources because of their rapid growth rates and high lipid cell content 2,3 , i.e. more than 50% of dry weight in some nutrient-limited microalgal species 4,5 . Microalgae-derived biodiesel is currently viewed as an appealing alternative for fossil fuels since the scale-up of algal biofuel production could be sufficient to meet at least 5% of U.S. demand for transportation fuels 6 . In addition, domestic production of renewable fuels including algal biofuels has the potential to meet the dual goals of improving energy security and decreasing greenhouse gas emissions from the transportation sector 3 . However, the production cost of biodiesel is still too high hampering large-scale commercialization of algae-derived biodiesel and new efficient strategies are urgently needed to increase economic viability of biodiesel production.Many studies have looked at the ecological and physiological factors regulating the production of lipids in autotrophic microalgae 1,3,7 . It is known that several environmental stressors (temperature, pH, salinity, and nutrient starvation) increase lipid cell quotas 8,9 . Nutrient starvation, nitrogen (N) especially proved to be one of the most successful approaches for enhancing lipid cell content in various microalgae species, such as Chlorella emersonii 10 (Trebouxiophyceae), Parietochloris incise 11 (chlorophyceae), Nannochloropsis spp 12 (Eustigmatophyceae), and Phaeodactylum tricornutum 7,13,14 (Bacillariophyceae). Although N starvation and other environmental stressors decrease algal growth rate and total lipid production, it has been suggested that a combination of optimal growth conditions and growth-limited conditions could help improve biodiesel production 3 . Another strategy that has the potential to improve the cost-effectiveness of biofuel production would be to overexpress key genes of fatty acid synthesis via genetic engineering 14 . Even though the study of Niu et al. 15 have shown that the overexpression of a type-2 diacylglycerol acyltransferase in a genetically engineered strain of a marine diato...

Trace aluminum (Al) concentrations can be toxic to marine phytoplankton, the basis of the marine food web, but the fundamental Al toxicity and detoxification mechanisms at the molecular levels are poorly understood. Using an array of proteomic, transcriptomic, and biochemical techniques, we describe in detail the cellular response of the model marine diatom Phaeodactylum tricornutum to a short-term sublethal Al stress (4 h of exposure to 200 μM total initial Al). A total of 2204 proteins were identified and quantified by isobaric tags for relative and absolute quantification (iTRAQ) in response to the Al stress. Among them, 87 and 78 proteins performing various cell functions were up- and down-regulated after Al treatment, respectively. We found that photosynthesis was a key Al toxicity target. The Al-induced decrease in electron transport rates in thylakoid membranes lead to an increase in reactive oxygen species (ROS) production, which cause increased lipid peroxidation. Several ROS-detoxifying proteins were induced to help decrease Al-induced oxidative stress. In parallel, glycolysis and pentose phosphate pathway were up-regulated in order to produce cell energy (NADPH, ATP) and carbon skeleton for cell growth, partially circumventing the Al-induced toxicity effects on photosynthesis. These cellular responses to Al stress were coordinated by the activation of various signal transduction pathways. The identification of Al-responsive proteins in the model marine phytoplankton P. tricornutum provides new insights on Al stress responses as well as a good start for further exploring Al detoxification mechanisms.

Bullous pemphigoid (BP), an autoimmune skin disease, is characterized by autoantibodies against hemidesmosomal proteins in the skin and mucous membranes. Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno‐inflammatory consequences. In the present study, we found that circulating NET‐related biomarker levels increased in serum and blister fluid of BP patients and significantly correlated with disease severity. Additionally, circulating neutrophils from BP patients displayed enhanced spontaneous NETs formation than healthy controls. In vitro, BP180‐NC16A immune complexes‐induced NETosis in neutrophils from BP patients, which was abrogated by Fcγ receptor and/or NADPH pathway blockade. Furthermore, the elevated levels of NETs from BP patients boosted autoantibody production by inducing B‐cell differentiation into plasma cells, mediated by MAPK P38 cascade activation. Together, our findings provide strong evidence that NETs are involved in a pathogenic loop, causing excessive differentiation of B cells and promotion of autoantibody production. Hence, targeting aberrant neutrophil responses will provide novel potential targets for the treatment of BP.

Dysfunction in the suppressive function of regulatory T cells (Tregs) has been related to the pathogenesis of psoriasis. Accumulating evidence has demonstrated the importance of circular RNAs (circRNAs) in regulating various biological process, such as cell proliferation, apoptosis, etc. However, the role of circR-NAs in modulating the suppressive functions of psoriatic Tregs and the underlying mechanisms have not been investigated. Here, by using circRNA microarray analysis, we discovered four upregulated and four downregulated circRNAs in psoriatic Tregs. Quantitative real-time PCR further confirmed a significant increase of circ_0003738 in psoriatic Tregs. Importantly, knockdown of circ_0003738 by lentivirus in psoriatic Tregs could restore their suppressive functions via inhibiting the secretion of proinflammatory cytokines interleukin-17A (IL-17A) and interferon (IFN)-g. Moreover, we found that circ_0003738 could bind to miR-562 to release the inhibition of target gene IL-17RA (IL-17 receptor A), thus promoting IL-17A signaling in psoriatic Tregs. In parallel, circ_0003738 acted also as a sponge for miR-490-5p and relieved inhibition for the target gene IFNGR2, which promoted IFN-g signaling in psoriatic Tregs. Our study demonstrated that upregulated circ_0003738 decreased the suppressive function of psoriatic Tregs via the miR-562/IL17RA and miR-490-5p/IFNGR2 (IFN-g receptor 2) axis, which indicated the involvement of circRNAs in the pathogenesis of dysfunctional Tregs. These findings will provide new therapeutic targets for the treatment of psoriasis.