Integrative taxonomy of the Pavlovophyceae (Haptophyta): a reassessment

The Pavlovophyceae (Haptophyta) contains four genera (Pavlova, Diacronema, Exanthemachrysis and Rebecca) and only thirteen characterised species, several of which are important in ecological and economic contexts. We have constructed molecular phylogenies inferred from sequencing of ribosomal gene markers with comprehensive coverage of the described diversity, using type strains when available, together with additional cultured strains. The morphology and ultrastructure of 12 of the described species was also re-examined and the pigment signatures of many culture strains were determined. The molecular analysis revealed that sequences of all described species differed, although those of Pavlova gyrans and P. pinguis were nearly identical, these potentially forming a single cryptic species complex. Four well-delineated genetic clades were identified, one of which included species of both Pavlova and Diacronema. Unique combinations of morphological/ultrastructural characters were identified for each of these clades. The ancestral pigment signature of the Pavlovophyceae consisted of a basic set of pigments plus MV chl cPAV, the latter being entirely absent in the Pavlova + Diacronema clade and supplemented by DV chl cPAV in part of the Exanthemachrysis clade. Based on this combination of characters, we propose a taxonomic revision of the class, with transfer of several Pavlova species to an emended Diacronema genus. The evolution of the class is discussed in the context of the phylogenetic reconstruction presented.     

Thyrsiferol Inhibits Mitochondrial Respiration and HIF-1 Activation

The cytotoxic marine red algal metabolite thyrsiferol (1) was found to inhibit hypoxia-induced hypoxia-inducible factor-1 (HIF-1) activation in T47D human breast tumor cells (66% inhibition at 3 μM). Compound 1 also suppressed hypoxic induction of HIF-1 target genes (VEGF, GLUT-1) at the mRNA level, and displayed tumor cell line-selective time-dependent inhibition of cell viability/proliferation. Mechanistic studies revealed that 1 selectively suppressed mitochondrial respiration at Complex I (IC(50) 3 μM). Thyrsiferol represents a prototypical, structurally unique electron transport chain inhibitor. The apparent rotenone-like activity may contribute to the observed cytotoxicity of 1 and play an important role in Laurencia chemical defense.     

Fumonisin production by <Emphasis Type="Italic">Fusarium</Emphasis> species isolated from freshly harvested corn in Iran

Fifty-one strains of Fusarium verticillioides and F. proliferatum isolated from corn collected from four different geographic areas in Iran, namely Fars, Khuzestan, Kermanshah and Mazandaran (an endemic oesophageal cancer (OC) area) were evaluated for their ability to produce fumonisins B₁ (FB₁), B₂ (FB₂) and B₃ (FB₃) in corn culture. Fumonisin levels were determined by high-performance liquid chromatography. All tested strains of F. verticillioides and F. proliferatumproduced fumonisins within a wide range of concentrations, 197–9661 g/g, 18–1974 g/g, and 21–1725 g/g for FB₁, FB₂, and FB₃, respectively. The highest mean concentrations of FB₁, FB₂, and FB₃ were 3897, 806 and 827 g/g, respectively. Overall, 61% of the F. verticillioides and F. proliferatum strains produced higher levels of FB₃ than FB₂. The mean ratios of FB₁:FB₂, FB₁:FB₃ and FB₁:total fumonisins were 8, 7 and 0.7 for F. verticillioides and 5.7, 10.7 and 0.7 for F. proliferatum, respectively. Significant differences in some of the meteorological data (rainfall, relative humidity and minimum temperature) from the four provinces were observed. Fumonisin levels produced by F. verticillioides strains isolated from Khuzestan province (tropical zone) were significantly (P < 0.01) higher than the other three provinces. This is the first report of the fumonisin-producing ability of F.verticillioides and F. proliferatum strains isolated from corn harvested from different geographic areas in Iran.     

Cell proliferation and STAT6 pathways are negatively regulated in T cells by STAT1 and suppressors of cytokine signaling

Suppressor of cytokine signaling (SOCS) proteins have emerged as important regulators of cytokine signals in lymphocytes. In this study, we have investigated regulation of SOCS expression and their role in Th cell growth and differentiation. We show that SOCS genes are constitutively expressed in naive Th cells, albeit at low levels, and are differentially induced by Ag and Th-polarizing cytokines. Whereas cytokines up-regulate expression of SOCS1, SOCS2, SOCS3, and cytokine-induced Src homology 2 protein, Ags induce down-regulation of SOCS3 within 48 h of Th cell activation and concomitantly up-regulate SOCS1, SOCS2, and cytokine-induced Src homology 2 protein expression. We further show that STAT1 signals play major roles in inducing SOCS expression in Th cells and that induction of SOCS expression by IL-4, IL-12, or IFN-gamma is compromised in STAT1-deficient primary Th cells. Surprisingly, IL-4 is a potent inducer of STAT1 activation in Th2 but not Th1 cells, and SOCS1 or SOCS3 expression is dramatically reduced in STAT1(-/-) Th2 cells. To our knowledge, this is the first report of IL-4-induced STAT1 activation in Th cells, and suggests that its induction of SOCS, may in part, regulate IL-4 functions in Th2 cells. In fact, overexpression of SOCS1 in Th2 cells represses STAT6 activation and profoundly inhibits IL-4-induced proliferation, while depletion of SOCS1 by an anti-sense SOCS1 cDNA construct enhances cell proliferation and induces constitutive activation of STAT6 in Th2 cells. These results are consistent with a model where IL-4 has dual effects on differentiating T cells: it simulates proliferation/differentiation through STAT6 and autoregulates its effects on Th2 growth and effector functions via STAT1-dependent up-regulation of SOCS proteins.     

The marine sponge metabolite mycothiazole: A novel prototype mitochondrial complex I inhibitor

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC₅₀ 1 nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP⁺, annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound with a central thiazole moiety. The exquisite potency and structural novelty of 1 suggest that it may serve as a valuable molecular probe for mitochondrial biology and HIF-mediated hypoxic signaling.     

Gastrointestinal nematode infection is associated with variation in innate immune responsiveness

Ex vivo monocyte cytokine responses (IL-1beta, TNF-alpha, IL-12p70, IL-10, TGF-beta) to bacterial TLR2 and TLR4 ligands were quantified in 47 gastrointestinal (GI) nematode-exposed children in Pemba Island, Tanzania. Worminess (estimated by faecal egg counts (FEC)) had a positive relationship with pro-inflammatory TNF-alpha and IL-1beta responsiveness to the TLR ligands. In particular, there was a strong significant relationship with TNF-alpha response to TLR4 ligand (LPS). There were no significant associations between regulatory responses (IL-10, TGF-beta) and worminess. These results are consistent with the possibility that GI nematodes modulate innate responses and may indicate a potential mechanism for interactions between GI nematodiasis and important bystander pathogens.     

Increase of autophagy and attenuation of apoptosis by Salvigenin promote survival of SH-SY5Y cells following treatment with H2O2

Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. Here, we tried to elucidate the possible neuroprotective effect of Salvigenin, a natural polyphenolic compound, on oxidative stress-induced apoptosis and autophagy in human neuroblastoma SH-SY5Y cells. We measured cell viability by MTT test and found that 25?μM is the best protective concentration of Salvigenin. GSH and SOD assays suggested that Salvigenin activates antioxidant factors. At the same time, measurement of ER stress-associated proteins including calpain and caspase-12 showed the ability of Salvigenin to decrease ER stress. We found that Salvigenin could decrease the apoptotic factors. Salvigenin inhibited H₂O₂-induced caspase-3 which is a hallmark of apoptosis in addition to reducing Bax\Bcl-2 ratio by 1.45 fold. Additionally, Salvigenin increased the levels of autophagic factors. Our results showed an increase in LC3-II/LC3-I ratio, Atg7, and Atg12 in the presence of 25?μM of Salvigenin by about 1.28, 1.25, and 1.54 folds, respectively, compared to H₂O₂-treated cells. So it seems that H₂O₂ cytotoxicity mainly results from apoptosis. Besides, Salvigenin helps cells to survive by inhibiting apoptosis and enhancing autophagy that opens a new horizon for the future experiments.