Characterization of a novel protein with homology to C-type lectins expressed by the Cotesia rubecula bracovirus in larvae of the lepidopteran host, Pieris rapae

Polydnaviruses are essential for the survival of many Ichneumonoid endoparasitoids, providing active immune suppression of the host in which parasitoid larvae develop. The Cotesia rubecula bracovirus is unique among polydnaviruses in that only four major genes are detected in parasitized host ( Pieris rapae) tissues, and gene expression is transient. Here we describe a novel C. rubecula bracovirus gene (CrV3) encoding a lectin monomer composed of 159 amino acids, which has conserved residues consistent with invertebrate and mammalian C-type lectins. Bacterially expressed CrV3 agglutinated sheep red blood cells in a divalent ion-dependent but Ca2+-independent manner. Agglutination was inhibited by EDTA but not by biological concentrations of any saccharides tested. Two monomers of similar to14 and similar to17 kDa in size were identified on SDS-PAGE in parasitized P. rapae larvae. The 17-kDa monomer was found to be an N-glyscosylated form of the 14-kDa monomer. CrV3 is produced in infected hemocytes and fat body cells and subsequently secreted into hemolymph. We propose that CrV3 is a novel lectin, the first characterized from an invertebrate virus. CrV3 shows over 60% homology with hypothetical proteins isolated from polydnaviruses in two other Cotesia wasps, indicating that these proteins may also be C-type lectins and that a novel polydnavirus lectin family exists in Cotesia-associated bracoviruses. CrV3 is probably interacting with components in host hemolymph, resulting in suppression of the Pieris immune response. The high similarity of CrV3 with invertebrate lectins, as opposed to those from viruses, may indicate that some bracovirus functions were acquired from their hosts.

Tomosyn interacts with the t-SNAREs Syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation

The Sec1p-like/Munc18 (SM) protein Munc18a binds to the neuronal t-SNARE Syntaxin1A and inhibits SNARE complex assembly. Tomosyn, a cytosolic Syntaxin1A-binding protein, is thought to regulate the interaction between Syntaxin1A and Munc18a, thus acting as a positive regulator of SNARE assembly. In the present study we have investigated the interaction between b-Tomosyn and the adipocyte SNARE complex involving Syntaxin4/SNAP23/VAMP-2 and the SM protein Munc18c, in vitro, and the potential involvement of Tomosyn in regulating the translocation of GLUT4 containing vesicles, in vivo. Tomosyn formed a high affinity ternary complex with Syntaxin4 and SNAP23 that was competitively inhibited by VAMP-2. Using a yeast two-hybrid assay we demonstrate that the VAMP-2-like domain in Tomosyn facilitates the interaction with Syntaxin4. Overexpression of Tomosyn in 3T3-L1 adipocytes inhibited the translocation of green fluorescent protein-GLUT4 to the plasma membrane. The SM protein Munc18c was shown to interact with the Syntaxin4 monomer, Syntaxin4 containing SNARE complexes, and the Syntaxin4/Tomosyn complex. These data suggest that Tomosyn and Munc18c operate at a similar stage of the Syntaxin4 SNARE assembly cycle, which likely primes Syntaxin4 for entry into the ternary SNARE complex.

Presence of the metabolic syndrome is associated with reduced adiponectin levels and liver dysfunction in patients with type 2 diabetes

No abstract.

Expression of the iron regulatory peptide hepcidin is reduced in patients with chronic liver disease

Disturbances in iron metabolism often accompany liver disease in humans and hepatic iron deposition is a frequent finding. Since the peptide hepcidin, a major regulator of body iron homeostasis, is synthesised in the liver, alterations in hepcidin expression could be responsible for these effects. To investigate this possibility, we studied hepcidin expression in liver biopsies from patients with hepatitis C virus (HCV) infection, non-alcoholic fatty liver disease (NAFLD) and hemochromatosis (HC). Total RNA was extracted from the liver tissue of 24 HCV, 17 NASH and 5 HC patients, and 17 liver transplant donors (controls). The levels of mRNA for hepcidin and several other molecules involved in iron metabolism (DMT1, Dcytb, hephaestin, ferroportin, TfR1, TfR2, HFE and HJV) were examined by ribonuclease protection assay and expressed relative to the housekeeping gene GAPDH. The expression of hepcidin was significantly decreased in HCV and NASH patients relative to control liver (109±16 and 200±44 versus 325±26 respectively; P=0.008 and 0.02). We have previously reported similar findings in patients with HC, and this was confirmed in the current analysis (176±21; P=0.003). In both HCV and NAFLD patients the expression of the iron reductase Dcytb and the transferrin binding regulatory molecule TfR2 was also decreased, while the cellular iron exporter ferroportin showed a significant increase. Levels of the mRNA for the iron oxidase hephaestin were lower in HCV patients alone, while expression of the major transferrin binding molecule TfR1 was decreased only in NAFLD patients. Of particular interest was the finding that the expression of HJV (which is mutated in patients with juvenile HC) was significantly increased in NAFLD patients. No changes were seen in the expression of the iron importer DMT1 or the regulatory molecule HFE. Decreased expression of hepcidin in patients with HCV and NAFLD provides an explanation why iron homeostasis could be perturbed in these disorders. Reduced hepcidin levels would increase intestinal iron absorption and iron release from macrophages, which could contribute to hepatic iron accumulation. This in turn could lead to alterations in the expression of various proteins involved in iron transport and its regulation. Indeed most of the changes in the expression of such molecules observed in this study are consistent with this. However, the mechanisms leading to changes in the expression of hepcidin in these diseases remain to be elucidated.

Proposal for the interaction of non-conventional partial agonists and catecholamines with the 'putative beta(4)-adrenoceptor' in mammalian heart

1. Evidence for a 'putative beta(4)-adrenoceptor' originated over 20 years ago when cardiostimulant effects were observed to nonconventional partial agonists, These agonists were originally described as beta(1)- and beta(2)-adrenoceptor antagonists; however, they cause cardiostimulant effects at much higher concentrations than those required to block beta(1)- and beta(2)-adrenoceptors. Cardiostimulant effects of non-conventional partial agonists have been observed in mouse, rat, guinea-pig, cat, ferret and human heart tissues, 2. The receptor is expressed in several heart regions, including the sinoatrial node, atrium and ventricle, 3. The receptor is resistant to blockade by most antagonists that possess high affinity for beta(1)- and beta(2)- adrenoceptors, but is blocked with moderate affinity by (-)-bupranolol and CGP 20712A. 4. The receptor is pharmacologically distinct from the beta(3)-adrenoceptor. Micromolar concentrations of beta(3)-adrenoceptor agonists have no agonist or blocking activity, The receptor is also resistant to blockade by a beta(3)-adrenoceptor-selective antagonist. 5. The receptor mediates increases in cAMP levels and cAMP-dependent protein kinase (PK) A activity in cardiac tissues. Phosphodiesterase inhibition potentiates the positive chronotropic and inotropic effects of non-conventional partial agonists. 6. The receptor mediates hastening of atrial and ventricular relaxation, which is consistent with involvement of a cAMP-dependent pathway. 7. The non-conventional partial agonist (-)-[H-3]-CGP 12177A labels the cardiac putative beta(4)-adrenoceptor, Non-conventional partial agonists compete for binding with affinities that are closely similar to their agonist potencies, Catecholamines compete for binding in a stereoselective manner with a rank order of affinity of (-)-R0363 > (-)-isoprenaline > (-)-noradrenaline greater than or equal to (-)-adrenaline much greater than (-)-isoprenaline, suggesting that catecholamines can interact with the receptor. 8. The putative beta(4)-adrenoceptor appears to be coupled to the G(s)-adenylyl cyclase system, which could serve as a guide to its future cloning, Activation of the receptor may plausibly improve diastolic function but could also mediate arrhythmias.

Performance impacts of appraisal and coping with stress in workplace settings: The role of affect and emotional intelligence

We review the literature on stress in organizational settings and, based on a model of job insecurity and emotional intelligence by Jordan, Ashkanasy and Härtel (2002), present a new model where affective responses associated with stress mediate the impact of workplace stressors on individual and organizational performance outcomes. Consistent with Jordan et al., emotional intelligence is a key moderating variable. In our model, however, the components of emotional intelligence are incorporated into the process of stress appraisal and coping. The chapter concludes with a discussion of the implications of these theoretical developments for understanding emotional and behavioral responses to workplace.

An investigation of the microstructure/electrical conductivity relationship in In2O3-substituted LSGM

The effect of controlled In3+ substitution on to the B-site in the perovskite oxygen ion conductor La0.9Sr0.1Ga0.8Mg0.2O2.85 (LSGM) has been examined with a view to exploring the influence on oxygen ion conductivity. In combination with the electrical conductivity study, detailed microstructural analysis was used to verify the location of the substituting cation and to determine the nature of secondary phase formation. The indium species clearly substituted for Ga3+ on the B-site of the lattice and the electrical conductivity showed a gradual decrease as the In+3 content increased. The interpretation of this data was complicated by the formation of the secondary phases LaInO3 and LaSrGaO4. (C) 2001 Elsevier Science Ltd. All rights reserved.

The application of electron microscopy and microanalysis in conjunction with organic petrology to further the understanding of organic-mineral association: examples from Mount Isa and McArthur Basins, Australia

Organic petrology supported by electron microscopical and micro-analytical techniques was applied to organic matter in Proterozoic sediments to better understand hydrothermal processes responsible for ore-grade mineralisation. It was shown that organic maturation was not only closely linked to the geological history of the sediments, but also highlighted heat transfer by convection as differentiated from conduction solely through sediment burial and step-wise subsidence. Water-rock ratios effect organic maturation in hydrothermal systems, and erratic reflectance profiles are indicators of convective heat transfer. Identification and characterisation of organic materials in terms of source rock and migrated hydrocarbons was shown to be a powerful tool in reconstructing the thermal history of sediments, identifying hydrothermal episodes, fluid pathways and heat source in the northern Australian Proterozoic basins. Higher reflectance of organic matter towards the central parts of the Mount Isa Basin and some of the most northerly parts point to proximity to higher heat flow at times, in contrast to relatively low temperatures prevailing in the western parts of the basin, next to the Murphy Inlier. A close correlation shown between peak organic reflectance values and super-sequence boundaries farther highlighted the valuable information to be gained from organic petrology, by allowing the separation of processes responsible for metal dissolution and transportation from those inducing precipitation. (C) 2001 Elsevier Science B.V All rights reserved.

Guadalupian algae-sponge reefs in siliciclastic environments - the reefs at Lengwu (South China) compared with the reef at Iwaizaki (Japan)

Guadalupian reefs occur locally in Guangxi, Guizhou, Yunnan and Western Zhejiang, South China. Two types of Guadalupian reefs can be recognized, one is developed in carbonate platforms, e.g. those in the juncture areas of Guangxi, Yunnan and Guizhou; the other occurs in a littoral clastic shelf. The Lengwu reef in Western Zhejiang is a representative of the latter type, which is a major topic of this paper. Lengwu algae-sponge reef, more than one hundred meters in thickness, are composed mainly of sponges, hydrozoans, algae, bryozoans, microbes and lime mud. Reef limestones sit on the mudstone interbedded with fine sandstone of the proximal prodelta facies and are overlain by coarse clasts of the delta front sediments. Lengwu reef displays a lens-shaped relief, dipping and thinning from the reef core, which is remarkably different from the surrounding sediments, showing a protruding relief. Sponges and microbe/algae form bafflestone, bindstone and framestone of the reef core facies. Fore-reef facies is characterized by lithoclastic rudstone and bioclastic packstone. Reef limestone sequence is composed of three cycles and controlled by sea level changes and sediment influx. Such reef is unique among the Guadalupian reefs in South China, but seems similar in some aspects to lwaizaki reef limestones of south Kitakami in Japan. Algae and microbes growing around sponges to form rigid structure in Lengwu reef are a typical feature, which is distinctly different to Guadalupian reefs in a stable platform facies of Guizhou, Yunnan and Guangxi, South China.