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Summary: Although mechanisms involved in response of Saccharomyces cerevisiae to osmotic challenge are well described for low and sudden stresses, little is known about how cells respond to a gradual increase of the osmotic pressure (reduced water activity; aw) over several generations as it could encounter during drying in nature or in food processes. Using glycerol as a stressor, we propagated S. cerevisiae through a ramp of the osmotic pressure (up to high molar concentrations to achieve testing‐to‐destruction) at the rate of 1.5 MPa day‐1 from 1.38 to 58.5 MPa (0.990–0.635 aw). Cultivability (measured at 1.38 MPa and at the harvest osmotic pressure) and glucose consumption compared with the corresponding sudden stress showed that yeasts were able to grow until about 10.5 MPa (0.926 aw) and to survive until about 58.5 MPa, whereas glucose consumption occurred until 13.5 MPa (about 0.915 aw). Nevertheless, the ramp conferred an advantage since yeasts harvested at 10.5 and 34.5 MPa (0.778 aw) showed a greater cultivability than glycerol‐shocked cells after a subsequent shock at 200 MPa (0.234 aw) for 2 days. FTIR analysis revealed structural changes in wall and proteins in the range 1.38–10.5 MPa, which would be likely to be involved in the resistance at extreme osmotic pressure. [ABSTRACT FROM AUTHOR]

Keywords: retrospective chart review; haemophilia A; immune tolerance induction; inhibitor; recombinant factor VIII Fc fusion protein; rescue therapy EN retrospective chart review haemophilia A immune tolerance induction inhibitor recombinant factor VIII Fc fusion protein rescue therapy 19 25 7 02/04/21 20210101 NES 210101 Dear Editor, Prophylactic factor VIII (FVIII) replacement is the current standard of care for severe haemophilia A but approximately 25%-40% of patients develop inhibitors against exogenous FVIII, rendering FVIII replacement therapy ineffective.1 Eradication of high-titre inhibitors involves immune tolerance induction (ITI): repeated, long-term administration of high-dose FVIII.1 Recombinant FVIII Fc fusion protein (rFVIIIFc [ELOCTATE SP ® sp , Sanofi, Waltham, MA]) is the first extended half-life FVIII approved for haemophilia A.2 Case reports and an initial retrospective chart review suggest that rFVIIIFc ITI may lead to faster tolerization than ITI with standard FVIII concentrates.3,4 This letter reports final clinical outcomes of 29 patients (19 included in the initial analysis) with severe haemophilia A undergoing ITI with rFVIIIFc in a real-world setting.4 We performed a retrospective review of patient charts at 13 sites across the United States and Canada, using previously published methods.4 Briefly, de-identified clinical data were collected from patients with severe haemophilia A and historical high-titre inhibitors, who began first-time or rescue ITI with rFVIIIFc between July 2014 and February 2018 and had >=3 months of exposure to rFVIIIFc ITI. Tolerization was defined as a negative Bethesda titre (<0.6 BU/mL), normal FVIII recovery (>=66% of expected) and rFVIIIFc half-life >=6 hours.5 Altogether, 29 rFVIIIFc ITI patients were identified: 10 first-time (Table 1) and 19 rescue patients (Table 2). [Extracted from the article]

Environmental heat stress impacts on the physiology and viability of microbial cells with concomitant implications for microbial activity and diversity. Previously, it has been demonstrated that gradual heating of S accharomyces cerevisiae induces a degree of thermal resistance, whereas a heat shock results in a high level of cell death. Here, we show that the impact of exogenous nutrients on acquisition of thermal resistance differs between strains. Using single-cell methods, we demonstrate the extent of heterogeneity of the heat-stress response within populations of yeast cells and the presence of subpopulations that are reversibly damaged by heat stress. Such cells represent potential for recovery of entire populations once stresses are removed. The results show that plasma membrane permeability and potential are key factors involved in cell survival, but thermal resistance is not related to homeoviscous adaptation of the plasma membrane. These results have implications for growth and regrowth of populations experiencing environmental heat stress and our understanding of impacts at the level of the single cell. Given the important role of microbes in biofuel production and bioremediation, a thorough understanding of the impact of stress responses of populations and individuals is highly desirable. [ABSTRACT FROM AUTHOR]

Ozone induces stomatal sluggishness, which impacts photosynthesis and transpiration. Stomatal responses to variation of environmental parameters are slowed and reduced by ozone and may be linked to difference of ozone sensitivity. Here we determine the ozone effects on stomatal conductance of each leaf surface. Potential causes of this sluggish movement, such as ultrastructural or ionic fluxes modification, were studied independently on both leaf surfaces of three Euramerican poplar genotypes differing in ozone sensitivity and in stomatal behaviour. The element contents in guard cells were linked to the gene expression of ion channels and transporters involved in stomatal movements, directly in microdissected stomata. In response to ozone, we found a decrease in the stomatal conductance of the leaf adaxial surface correlated with high calcium content in guard cells compared with a slight decrease on the abaxial surface. No ultrastructural modifications of stomata were shown except an increase in the number of mitochondria. The expression of vacuolar H+/Ca2+-antiports ( CAX1 and CAX3 homologs), β-carbonic anhydrases ( β CA1 and β CA4) and proton H+- ATPase ( AHA11) genes was strongly decreased under ozone treatment. The sensitive genotype characterized by constitutive slow stomatal response was also characterized by constitutive low expression of genes encoding vacuolar H+/Ca2+-antiports. [ABSTRACT FROM AUTHOR]

Cell capacity for cytosolic NADPH regeneration by NADP-dehydrogenases was investigated in the leaves of two hybrid poplar ( Populus deltoides × Populus nigra) genotypes in response to ozone ( O3) treatment (120 ppb for 17 days). Two genotypes with differential O3 sensitivity were selected, based on visual symptoms and fallen leaves: Robusta (sensitive) and Carpaccio (tolerant). The estimated O3 flux ( POD0), that entered the leaves, was similar for the two genotypes throughout the treatment. In response to that foliar O3 flux, CO2 assimilation was inhibited to the same extent for the two genotypes, which could be explained by a decrease in Rubisco ( EC 4.1.1.39) activity. Conversely, an increase in PEPC ( EC 4.1.1.31) activity was observed, together with the activation of certain cytosolic NADP-dehydrogenases above their constitutive level, i.e. NADP-G6PDH ( EC 1.1.1.49), NADP-ME (malic enzyme) ( EC 1.1.1.40) and NADP-ICDH (NADP-isocitrate dehydrogenase) ( EC1.1.1.42). However, the activity of non-phosphorylating NADP-GAPDH ( EC 1.2.1.9) remained unchanged. From the 11th fumigation day, NADP-G6PDH and NADP-ME profiles made it possible to differentiate between the two genotypes, with a higher activity in Carpaccio than in Robusta. At the same time, Carpaccio was able to maintain high levels of NADPH in the cells, while NADPH levels decreased in Robusta O3-treated leaves. All these results support the hypothesis that the capacity for cells to regenerate the reducing power, especially the cytosolic NADPH pool, contributes to improve tolerance to high ozone exposure. [ABSTRACT FROM AUTHOR]