Active role of the mucilage in the toxicity mechanism of the harmful benthic dinoflagellate Ostreopsis cf. ovata.

Ostreopsis cf. ovata is a harmful benthic dinoflagellate, widespread along most of the Mediterranean coasts. It produces a wide range of palytoxin-like compounds and variable amounts of mucus that may totally cover substrates, especially during the stationary phase of blooms. Studies on different aspects of the biology and ecology of Ostreopsis spp. are increasing, yet knowledge on toxicity mechanism is still limited. In particular, the potential active role of the mucilaginous matrix has not yet been shown, although when mass mortalities have occurred, organisms have been reported to be covered by the typical brownish mucilage. In order to better elucidate toxicity dependence on direct/indirect contact, the role of the mucilaginous matrix and the potential differences in toxicity along the growth curve of O. cf. ovata, we carried out a toxic bioassay during exponential, stationary and late stationary phases. Simultaneously, a molecular assay was performed to quantify intact cells or to exclude cells presence. A liquid chromatography – high resolution mass spectrometry (LC-HRMS) analysis was also carried out to evaluate toxin profile and content in the different treatments. Our results report higher mortality of model organism, especially during the late stationary phase, when direct contact between a model organism and intact microalgal cells occurs (LC50-48h <4 cells/ml on Artemia salina). Also growth medium devoid of microalgal cells but containing O. cf. ovata mucilage caused significant toxic effects. This finding is also supported by chemical analysis which shows the highest toxin content in pellet extract (95%) and around 5% of toxins in the growth medium holding mucous, while the treatment devoid of both cells and mucilage did not contain any detectable toxins. Additionally, the connection between mucilaginous matrix and thecal plates, pores and trychocysts was explored by way of atomic force microscopy (AFM) to investigate the cell surface at a sub-nanometer resolution, providing a pioneering description of cellular features

High resolution computed tomography quantitation of emphysema is correlated with selected lung function values in stable COPD.

BACKGROUND: The literature shows conflicting results when high-resolution computed tomography (HRCT) scores of emphysema were correlated with different indices of airflow obstruction. OBJECTIVES: We correlated HRCT scores of emphysema with different indices of airflow obstruction. METHODS: We performed HRCT of the chest in 59 patients, all smokers or ex-smokers, with stable chronic obstructive pulmonary disease of different severity [GOLD stages I-IV; mean age \ub1 SD 67.8 \ub1 7.3 years; pack/years 51.0 \ub1 34.6; percent predicted forced expiratory volume in 1 s (FEV(1)% predicted) 52.3 \ub1 17.6; post-bronchodilator FEV(1)% predicted 56.5 \ub1 19.1; FEV(1)/forced vital capacity (FVC) ratio 50.8 \ub1 10.2; post-bronchodilator FEV(1)/FVC ratio 51.6 \ub1 11.0; percent diffusion lung capacity for carbon monoxide (DLCO%) 59.2 \ub1 21.1; DLCO/percent alveolar volume (VA%) 54.5 \ub1 18.2; percent residual volume 163.0 \ub1 35.6; percent total lung capacity (TLC%) 113.2 \ub1 15; residual volume/TLC 1.44 \ub1 0.2]. All patients were in stable phase. RESULTS: The mean \ub1 SD visual emphysema score in all patients was 25.6 \ub1 25.4%. There was a weak but significant correlation between the percentage of pulmonary emphysema and numbers of pack/years (R = +0.31, p = 0.024). The percentage of emphysema was inversely correlated with the FEV(1)/FVC ratio before and after bronchodilator use (R = -0.44, p = 0.002, and R = -0.39, p = 0.005), DLCO% (R = -0.64, p = 0.0003) and DLCO/VA% (R = -0.68, p < 0.0001). A weak positive correlation was also found with TLC% (R = +0.28, p = 0.048). When patients with documented emphysema were considered separately, the best significant correlation observed was between DLCO/VA% and HRCT scan score (p = 0.007). CONCLUSIONS: These data suggest that in patients with stable chronic obstructive pulmonary disease of varying severity, the presence of pulmonary emphysema is best represented by the impaired gas exchange capability of the respiratory system

A coumaroyl-ester-3-hydroxylase insertion mutant reveals the existence of nonredundant meta-hydroxylation pathways and essential roles for phenolic precursors in cell expansion and plant growth

Cytochromes P450 monooxygenases from the CYP98 family catalyze the meta-hydroxylation step in the phenylpropanoid biosynthetic pathway. The ref8 Arabidopsis (Arabidopsis thaliana) mutant, with a point mutation in the CYP98A3 gene, was previously described to show developmental defects, changes in lignin composition, and lack of soluble sinapoyl esters. We isolated a T-DNA insertion mutant in CYP98A3 and show that this mutation leads to a more drastic inhibition of plant development and inhibition of cell growth. Similar to the ref8 mutant, the insertion mutant has reduced lignin content, with stem lignin essentially made of p-hydroxyphenyl units and trace amounts of guaiacyl and syringyl units. However, its roots display an ectopic lignification and a substantial proportion of guaiacyl and syringyl units, suggesting the occurrence of an alternative CYP98A3-independent meta-hydroxylation mechanism active mainly in the roots. Relative to the control, mutant plantlets produce very low amounts of sinapoyl esters, but accumulate flavonol glycosides. Reduced cell growth seems correlated with alterations in the abundance of cell wall polysaccharides, in particular decrease in crystalline cellulose, and profound modifications in gene expression and homeostasis reminiscent of a stress response. CYP98A3 thus constitutes a critical bottleneck in the phenylpropanoid pathway and in the synthesis of compounds controlling plant development. CYP98A3 cosuppressed lines show a gradation of developmental defects and changes in lignin content (40% reduction) and structure (prominent frequency of p-hydroxyphenyl units), but content in foliar sinapoyl esters is similar to the control. The purple coloration of their leaves is correlated to the accumulation of sinapoylated anthocyanins

First-Phase Insulin Secretion Restoration and Differential Response to Glucose Load Depending on the Route of Administration in Type 2 Diabetic Subjects After Bariatric Surgery

OBJECTIVE—The purpose of this study was to elucidate the mechanisms of diabetes reversibility after malabsorptive bariatric surgery

Maximizing the Products Display for Purchaser Lucidity and Alleviation in Circulation to Augment the Sale of Supermarket: Milieu of Bangladesh

The purpose of this study is to appraise the accessible products display for the purchaser lucidity which may maximizes offers and actions of business with the alleviation in circulation to augment the random sale in the arena of supermarket. The study scrutinizes a fundamental research on the context of Bangladesh and especially for the Dhaka zone. A supermarket, a large form of the traditional grocery store, is a self-service shop offering a wide variety of food and household products, organized into aisles. It is larger in size and has a wider selection than a traditional grocery store, but is smaller and more limited in the range of merchandise than a hypermarket or big-box market. The traditional supermarket occupies a large amount of floor space, usually on a single level. It is usually situated near a residential area in order to be convenient to consumers. The basic appeal is the availability of a broad selection of goods under a single roof, at relatively low prices. Other advantages include ease of parking and frequently the convenience of shopping hours that extend far into the evening or even 24 hours a day. Key words: Circulation, Supermarket, Alleviation, Sale, Products, Variation, Lucidit

The Transforming Growth Factor-β Pathway Is a Common Target of Drugs That Prevent Experimental Diabetic Retinopathy

OBJECTIVE-- Prevention of diabetic retinopathy would benefit from availability of drugs that preempt the effects of hyperglycemia on retinal vessels. We aimed to identify candidate drug targets by investigating the molecular effects of drugs that prevent retinal capillary demise in the diabetic rat. RESEARCH DESIGN AND METHODS-- We examined the gene expression profile of retinal vessels isolated from rats with 6 months of streptozotocin-induced diabetes and compared it with that of control rats. We then tested whether the aldose reductase inhibitor sorbinil and aspirin, which have different mechanisms of action, prevented common molecular abnormalities induced by diabetes. The Affymetrix GeneChip Rat Genome 230 2.0 array was complemented by real-time RT-PCR, immunoblotting, and immunohistochemistry. RESULTS-- The retinal vessels of diabetic rats showed differential expression of 20 genes of the transforming growth factor (TGF)-β pathway, in addition to genes involved in oxidative stress, inflammation, vascular remodeling, and apoptosis. The complete loop of TGF-β signaling, including Smad2 phosphorylation, was enhanced in the retinal vessels, but not in the neural retina. Sorbinil normalized the expression of 71% of the genes related to oxidative stress and 62% of those related to inflammation. Aspirin had minimal or no effect on these two categories. The two drugs were instead concordant in reducing the upregulation of genes of the TGF-β pathway (55% for sorbinil and 40% for aspirin) and apoptosis (74 and 42%, respectively). CONCLUSIONS-- Oxidative and inflammatory stress is the distinct signature that the polyol pathway leaves on retinal vessels. TGF-β and apoptosis are, however, the ultimate targets to prevent the capillary demise in diabetic retinopathy

Future HAB science: Directions and challenges in a changing climate

There is increasing concern that accelerating environmental change attributed to human-induced warming of the planet may substantially alter the patterns, distribution and intensity of Harmful Algal Blooms (HABs). Changes in temperature, ocean acidification, precipitation, nutrient stress or availability, and the physical structure of the water column all influence the productivity, composition, and global range of phytoplankton assemblages, but large uncertainty remains about how integration of these climate drivers might shape future HABs. Presented here are the collective deliberations from a symposium on HABs and climate change where the research challenges to understanding potential linkages between HABs and climate were considered, along with new research directions to better define these linkages. In addition to the likely effects of physical (temperature, salinity, stratification, light, changing storm intensity), chemical (nutrients, ocean acidification), and biological (grazer) drivers on microalgae (senso lato), symposium participants explored more broadly the subjects of cyanobacterial HABs, benthic HABs, HAB effects on fisheries, HAB modelling challenges, and the contributions that molecular approaches can bring to HAB studies. There was consensus that alongside traditional research, HAB scientists must set new courses of research and practices to deliver the conceptual and quantitative advances required to forecast future HAB trends. These different practices encompass laboratory and field studies, long-term observational programs, retrospectives, as well as the study of socioeconomic drivers and linkages with aquaculture and fisheries. In anticipation of growing HAB problems, research on potential mitigation strategies should be a priority. It is recommended that a substantial portion of HAB research among laboratories be directed collectively at a small sub-set of HAB species and questions in order to fast-track advances in our understanding. Climate-driven changes in coastal oceanographic and ecological systems are becoming substantial, in some cases exacerbated by localized human activities. That, combined with the slow pace of decreasing global carbon emissions, signals the urgency for HAB scientists to accelerate efforts across disciplines to provide society with the necessary insights regarding future HAB trends

Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue inhibitor of metalloproteinase-1 are associated with vascular complications in patients with type 1 diabetes: The EURODIAB Prospective Complications Study

Impaired regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in patients with type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular disease (CVD) or microvascular complications in type 1 diabetic patients. We also evaluated to which extent these associations could be explained by low-grade inflammation (LGI) or endothelial dysfunction (ED). Methods: 493 type 1 diabetes patients (39.5 ± 9.9 years old, 51% men) from the EURODIAB Prospective Complications Study were included. Linear regression analysis was applied to investigate differences in plasma levels of MMP-1, -2, -3, -9, -10, and TIMP-1 between patients with and without CVD, albuminuria or retinopathy. All analyses were adjusted for age, sex, duration of diabetes, Hba1c and additionally for other cardiovascular risk factors including LGI and ED. Results: Patients with CVD (n = 118) showed significantly higher levels of TIMP-1 [β = 0.32 SD (95%CI: 0.12; 0.52)], but not of MMPs, than patients without CVD (n = 375). Higher plasma levels of MMP-2, MMP-3, MMP-10 and TIMP-1 were associated with higher levels of albuminuria (p-trends were 0.028, 0.004, 0.005 and 0.001, respectively). Severity of retinopathy was significantly associated with higher levels of MMP-2 (p-trend = 0.017). These associations remained significant after further adjustment for markers of LGI and ED. Conclusions: These data support the hypothesis that impaired regulation of matrix remodeling by actions of MMP-2, -3 and-10 and TIMP-1 contributes to the pathogenesis of vascular complications in type 1 diabetes

Influenza Virus Non-Structural Protein 1 (NS1) Disrupts Interferon Signaling

Type I interferons (IFNs) function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1) encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1-, STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non-tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1 virus infection of human monocyte-derived macrophages led to inhibition of both ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo human lung tissues with IFN-α results in the up-regulation of a number of IFN-stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data suggest that NS1 can directly interfere with IFN signaling to enhance viral replication, but that treatment with IFN can nevertheless override these inhibitory effects to block H5N1 and H1N1 virus infections