Role of Pneumococcal NanA Neuraminidase Activity in Peripheral Blood

The most frequent form of hemolytic-uremic syndrome (HUS) is associated with infections caused by Shiga-like toxin-producing Enterohaemorrhagic Escherichia coli (STEC). In rarer cases HUS can be triggered by Streptococcus pneumoniae. While production of Shiga-like toxins explains STEC-HUS, the mechanisms of pneumococcal HUS are less well known. S. pneumoniae produces neuraminidases with activity against cell surface sialic acids that are critical for factor H-mediated complement regulation on cells and platelets. The aim of this study was to find out whether S. pneumoniae neuraminidase NanA could trigger complement activation and hemolysis in whole blood. We studied clinical S. pneumoniae isolates and two laboratory strains, a wild-type strain expressing NanA, and a NanA deletion mutant for their ability to remove sialic acids from various human cells and platelets. Red blood cell lysis and activation of complement was measured ex vivo by incubating whole blood with bacterial culture supernatants. We show here that NanA expressing S. pneumoniae strains and isolates are able to remove sialic acids from cells, and platelets. Removal of sialic acids by NanA increased complement activity in whole blood, while absence of NanA blocked complement triggering and hemolytic activity indicating that removal of sialic acids by NanA could potentially trigger pHUS.Peer reviewe

Differential gene expression between wild-type and Gulo-deficient mice supplied with vitamin C

The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-gulonolactone oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n = 3 for each group), respectively. Total hepatic RNA was used in triplicate microarray assays for each group. EDGE software was used to identify differentially expressed genes and transcriptomic analysis was used to assess the potential genetic regulation of Gulo gene expression. Hepatic VC concentrations in MT mice were significantly lower than in WT mice, even though there were no morphological differences between the two groups. In MT mice, 269 differentially expressed transcripts were detected (≥ twice the difference between MT and WT mice), including 107 up-regulated and 162 down-regulated genes. These differentially expressed genes included stress-related and exclusively/predominantly hepatocyte genes. Transcriptomic analysis identified a major locus on chromosome 18 that regulates Gulo expression. Since three relevant oxidative genes are located within the critical region of this locus we suspect that they are involved in the down-regulation of oxidative activity in sfx mice

Gradients of anthropogenic nutrient enrichment alter N Composition and DOM stoichiometry in freshwater ecosystems

Plain language summary Ammonium and nitrate in freshwaters have received considerable attention due to their clear ecological and health effects. A comprehensive assessment of N in freshwaters that includes DON is lacking. Including DON in studies of surface water chemistry is important because it can cause eutrophication and certain forms can be rapidly removed by microbial communities. Here, we document how elevated levels of TDN impact the concentrations and relative proportions of all three forms of dissolved N and the stoichiometry of DOM. Our results suggest that human activities fundamentally alter the composition of the dissolved nitrogen pool and the stoichiometry of DOM. Results also highlight feedbacks between the C and N cycles in freshwater ecosystems that are poorly studied.A comprehensive cross-biome assessment of major nitrogen (N) species that includes dissolved organic N (DON) is central to understanding interactions between inorganic nutrients and organic matter in running waters. Here, we synthesize stream water N chemistry across biomes and find that the composition of the dissolved N pool shifts from highly heterogeneous to primarily comprised of inorganic N, in tandem with dissolved organic matter (DOM) becoming more N-rich, in response to nutrient enrichment from human disturbances. We identify two critical thresholds of total dissolved N (TDN) concentrations where the proportions of organic and inorganic N shift. With low TDN concentrations (0–1.3 mg/L N), the dominant form of N is highly variable, and DON ranges from 0% to 100% of TDN. At TDN concentrations above 2.8 mg/L, inorganic N dominates the N pool and DON rarely exceeds 25% of TDN. This transition to inorganic N dominance coincides with a shift in the stoichiometry of the DOM pool, where DOM becomes progressively enriched in N and DON concentrations are less tightly associated with concentrations of dissolved organic carbon (DOC). This shift in DOM stoichiometry (defined as DOC:DON ratios) suggests that fundamental changes in the biogeochemical cycles of C and N in freshwater ecosystems are occurring across the globe as human activity alters inorganic N and DOM sources and availability. Alterations to DOM stoichiometry are likely to have important implications for both the fate of DOM and its role as a source of N as it is transported downstream to the coastal ocean

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p

Effects of differential rates of alternative reinforcement on resurgence of human behavior

Despite the success of exposure-based psychotherapies in anxiety treatment, relapse remains problematic. Resurgence, the return of previously eliminated behavior following the elimination of an alternative source of reinforcement, is a promising model of operant relapse. Nonhuman resurgence research has shown that higher rates of alternative reinforcement result in faster, more comprehensive suppression of target behavior, but also in greater resurgence when alternative reinforcement is eliminated. This study investigated rich and lean rates of alternative reinforcement on response suppression and resurgence in typically developing humans. In Phase 1, three groups (Rich, n = 18; Lean, n = 18; Control, n = 10) acquired the target response. In Phase 2, target responding was extinguished and alternative reinforcement delivered on RI 1 s, RI 3 s, and extinction schedules, respectively. Resurgence was assessed during Phase 3 under extinction conditions for all groups. Target responding was suppressed most thoroughly in Rich and partially in Lean. Target responding resurged in the Rich and Lean groups, but not in the Control group. Between groups, resurgence was more pronounced in the Rich group than the Lean and Control groups. Clinical implications of these findings, including care on the part of clinicians when identifying alternative sources of reinforcement, are discussed