Modulation of Protease Activated Receptor 1 Influences Human Metapneumovirus Disease Severity in a Mouse Model

Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.     

Economic activity in the South-Asian population in Britain: the impact of ethnicity,religion, and class

This paper expands the existing literature on ethnicity and economic activity in Britain by studying the impact of religion and class. It argues that while the class location of the different South-Asian groups is important in determining their labour market outcomes, it does not operate independently from ethnicity; rather it is highly influenced by ethnicity in the process of determining the labour market participation of these groups. We use data obtained from the 2001 UK Census on Indian, Pakistani, and Bangladeshi men and women aged between twenty and twenty nine. Our findings confirm that class structure of the South-Asian groups is highly ethnicized, in that the ethno-religious background and class are interwoven to the extent that the separation between them is not easy, if not impossible.     

Application of high-voltage electrical discharges and high-pressure homogenization for recovery of intracellular compounds from microalgae Parachlorella kessleri

Treatments with high-voltage electrical discharges (HVED) and high-pressure homogenization (HPH) were studied and compared for the release of ionic components, carbohydrates, proteins, and pigments from microalgae Parachlorella kessleri (P. kessleri). Suspensions (1% w/w) of microalgae were treated by HVED (40 kV/cm, 1–8 ms) or by HPH (400–1200 bar, 1–10 passes). Particle-size distribution (PSD) and microscopic analyses were used to detect the disruption and damage of cells. HVED were very effective for the extraction of ionic cell components and carbohydrates (421 mg/L after 8 ms of the treatment). However, HVED were ineffective for pigments and protein extraction. The concentration of proteins extracted by HVED was just 750 mg/L and did not exceed 15% of the total quantity of proteins. HPH permitted an effective release overall of intracellular compounds from P. kessleri microalgae including a large quantity of proteins, whose release (at 1200 bar) was 4.9 times higher than that obtained by HVED. Consequently, HVED can be used at the first step of the overall extraction process for the selective recovery of low-molecular-weight components. HPH can be then used at the second step for the recovery of remaining cell compounds.

     

Emerging techniques for cell disruption and extraction of valuable bio-molecules of microalgae Nannochloropsis sp.

Bioprocess and Biosystems Engineering - Microalgae of Nannochloropsis sp. present valuable source of bio-molecules (pigments, lipids, proteins) that have nutritional potential for the...     

Tolerance of free‐living nematode species to imidacloprid and diuron

The neonicotinoid imidacloprid and the herbicide diuron are long‐lived pesticides commonly detected in European rivers. Both have lethal as well as sublethal effects on aquatic invertebrates dwelling in streambeds. Here, we performed lethality tests of imidacloprid and diuron on seven species of widespread, free‐living nematodes and the model organism Caenorhabditis elegans. Our results indicated that nematodes were relatively tolerant to both pesticides, and only two species (Diploscapter coronatus and Plectus opisthocirculus) showed mortality at high nominal concentrations of imidacloprid (119 mg/L) and diuron (33 mg/L). The changes observed in nematode community structure after imidacloprid and diuron exposure may have been related to trade‐offs between sensitivity to toxicants and changes in competitive abilities of the species. While the former can be tested using single‐species tests, we recommend that the latter be tested in further experiments using multispecies communities. Our results suggest that the presence of these pesticides could favor nematodes over other meiofaunal groups found in freshwater sediments.     

Distinct Mycobacterium marinum phosphatases determine pathogen vacuole phosphoinositide pattern,phagosome maturation,and escape to the cytosol

The causative agent of tuberculosis, Mycobacterium tuberculosis, and its close relative Mycobacterium marinum manipulate phagocytic host cells, thereby creating a replication‐permissive compartment termed the Mycobacterium‐containing vacuole (MCV). The phosphoinositide (PI) lipid pattern is a crucial determinant of MCV formation and is targeted by mycobacterial PI phosphatases. In this study, we establish an efficient phage transduction protocol to construct defined M. marinum deletion mutants lacking one or three phosphatases, PtpA, PtpB, and/or SapM. These strains were defective for intracellular replication in macrophages and amoebae, and the growth defect was complemented by the corresponding plasmid‐borne genes. Fluorescence microscopy of M. marinum‐infected Dictyostelium discoideum revealed that MCVs harbouring mycobacteria lacking PtpA, SapM, or all three phosphatases accumulate significantly more phosphatidylinositol‐3‐phosphate (PtdIns3P) compared with MCVs containing the parental strain. Moreover, PtpA reduced MCV acidification by blocking the recruitment of the V‐ATPase, and all three phosphatases promoted bacterial escape from the pathogen vacuole to the cytoplasm. In summary, the secreted M. marinum phosphatases PtpA, PtpB, and SapM determine the MCV PI pattern, compartment acidification, and phagosomal escape.     

Respiratory distress and neonatal lethality in mice lacking Golgi alpha1,2-mannosidase IB involved in N-glycan maturation

There are three mammalian Golgi alpha1,2-mannosidases, encoded by different genes, that form Man5GlcNAc2 from Man(8-9)GlcNAc2 for the biosynthesis of hybrid and complex N-glycans. Northern blot analysis and in situ hybridization indicate that the three paralogs display distinct developmental and tissue-specific expression. The physiological role of Golgi alpha1,2-mannosidase IB was investigated by targeted gene ablation. The null mice have normal gross appearance at birth, but they display respiratory distress and die within a few hours. Histology of fetal lungs the day before birth indicate some delay in development, whereas neonatal lungs show extensive pulmonary hemorrhage in the alveolar region. No significant histopathological changes occur in other tissues. No remarkable ultrastructural differences are detected between wild type and null lungs. The membranes of a subset of bronchiolar epithelial cells are stained with lectins from Phaseolus vulgaris (leukoagglutinin and erythroagglutinin) and Datura stramonium in wild type lungs, but this staining disappears in lungs from null mice. Mass spectrometry of N-glycans from different tissues shows no significant changes in global N-glycans of null mice. Therefore, only a few glycoproteins required for normal lung function depend on alpha1,2-mannosidase IB for maturation. There are no apparent differences in the expression of several lung epithelial cell and endothelial cell markers between null and wild type mice. The alpha1,2-mannosidase IB null phenotype differs from phenotypes caused by ablation of other enzymes in N-glycan biosynthesis and from other mouse gene disruptions that affect pulmonary development and function.     

Effects of the methanolic extract of Chrysanthemum trifurcatum (Desf.) Batt. and Trab. on rat duodenal motility

The effect of the methanolic extract of flowers of Chrysanthemum trifurcatum (Desf.) Batt. and Trab. Var. macrocephalum (viv.) Beg. on the rat duodenum smooth muscle motility was examined in vitro. The extract has shown dose-dependent stimulator effects on the amplitude of the spontaneous contractions. With 0.1 g/ml of extract, maximal stimulation was obtained. With that dose, the variation (%) was significantly 1050 +/- 13 (P<0.001) compared with control and represented 80 +/- 5.83% (P<0.001) of the maximum effect of acetylcholine. Atropine (2 microg/ml) reduced by 81 +/- 4% (P<0.05) the spasmogenic effects of C. trifurcatum and by 92 +/- 3% (P<0.05) the acetylcholine effects, while papaverine (2 microg/ml) completely inhibited the spasmogenic effects of extract. With a fixed dose of acetylcholine added (20 microg/ml), the extract increases its effect, but acetylcholine decreases its action. These results suggested that the methanolic extract of C. trifurcatum could stimulate duodenal smooth muscle contractions through muscarinic receptors. Thy explain the respective traditional use of plant in gastrointestinal problems, especially constipation.