The laminin β1-competing peptide YIGSR induces a hypercontractile,hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

Background

Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM) mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hyper)contractile phenotype is dependent on laminin, which can be inhibited by the laminin-competing peptide Tyr-Ile-Gly-Ser-Arg (YIGSR). The role of laminins in ASM remodelling in chronic asthma in vivo, however, has not yet been established.

Methods

Using an established guinea pig model of allergic asthma, we investigated the effects of topical treatment of the airways with YIGSR on features of airway remodelling induced by repeated allergen challenge, including ASM hyperplasia and hypercontractility, inflammation and fibrosis. Human ASM cells were used to investigate the direct effects of YIGSR on ASM proliferation in vitro.

Results

Topical administration of YIGSR attenuated allergen-induced ASM hyperplasia and pulmonary expression of the proliferative marker proliferating cell nuclear antigen (PCNA). Treatment with YIGSR also increased both the expression of sm-MHC and ASM contractility in saline- and allergen-challenged animals; this suggests that treatment with the laminin-competing peptide YIGSR mimics rather than inhibits laminin function in vivo. In addition, treatment with YIGSR increased allergen-induced fibrosis and submucosal eosinophilia. Immobilized YIGSR concentration-dependently reduced PDGF-induced proliferation of cultured ASM to a similar extent as laminin-coated culture plates. Notably, the effects of both immobilized YIGSR and laminin were antagonized by soluble YIGSR.

Conclusion

These results indicate that the laminin-competing peptide YIGSR promotes a contractile, hypoproliferative ASM phenotype in vivo, an effect that appears to be linked to the microenvironment in which the cells are exposed to the peptide.     

Proteome analysis of human Wharton's jelly cells during <Emphasis Type="Italic">in vitro</Emphasis> expansion

Background  

The human umbilical cord contains mucoid connective tissue and fibroblast-like cells. These cells named Wharton's jelly cells, (WJCs) display properties similar to mesenchymal stem cells therefore representing a rich source of primitive cells to be potentially used in regenerative medicine.     

Diversity, distribution and ecology of water mites (Acari: Hydrachnidia and Halacaridae) in high Alpine lakes (Central Alps, Italy)

Information on water mite assemblages from high elevation lentic biotopes is scant. A survey of 14 small Alpine lakes located between1900 and 2400 m a.s.l. in Italy resulted in the discovery of 17 species of Hydrachnidia and a single species of freshwater Halacaridae. Arrenurus conicus and Lebertia tuberosa were the most widespread and abundant species; Lebertia sefvei, Lebertia rufipes, Oxus setosus, Panisus torrenticolus and Sperchon glandulosus were also widely distributed but relatively less abundant. Atractides fissus and Arrenurus conicus are recorded for the first time from Italy. In contrast to mid/low elevation lakes and ponds, water mite assemblages of alpine lakes are less diverse and are composed mainly of rheo- and crenobiontic taxa, most of which are cold-stenothermic. Typical standing water dwellers represented only a small fraction (23%) of the species sampled. A principal component analysis conducted on lake environmental variables resulted in a clear separation of the lakes mainly based on ionic contents, pH and temperature. Water mites seem to be less influenced by these factors than by temperature fluctuations and habitat stability and heterogeneity. We conclude with some considerations of the influence of abiotic and biotic factors on the altitudinal and latitudinal distribution pattern of water mites.     

MalariaSphere: A greenhouse-enclosed simulation of a natural Anopheles gambiae (Diptera: Culicidae) ecosystem in western Kenya

Background  

The development and implementation of innovative vector control strategies for malaria control in Africa requires in-depth ecological studies in contained semi-field environments. This particularly applies to the development and release of genetically-engineered vectors that are refractory to Plasmodium infection. Here we describe a modified greenhouse, designed to simulate a natural Anopheles gambiae Giles ecosystem, and the first successful trials to complete the life-cycle of this mosquito vector therein.     

Global diversity of water mites (Acari,Hydrachnidia; Arachnida) in freshwater

The Hydrachnidia (water mites) represent the most important group of the Arachnida in fresh water. Over 6,000 species have been described worldwide, representing 57 families, 81 subfamilies and more than 400 genera. The article analyzes extant water mite diversity and biogeography. Data on distribution and species richness of water mites are substantial but still far from complete. Many parts of the world are poorly investigated, Oriental and Afrotropical regions in particular. Moreover, information among different freshwater habitats is unbalanced with springs and interstitial waters disproportionately unrepresented. Therefore, more than 10,000 species could be reasonably expected to occur in inland waters worldwide. Based on available information, the Palaearctic region represents one of the better investigated areas with the highest number of species recorded (1,642 species). More than 1,000 species have been recorded in each of the Neotropical (1,305 species) and Nearctic regions (1,025 species). Known species richness is lower in Afrotropical (787 species) and Australasian (694 species) regions, and lowest in the Oriental region (554 species). The total number of genera is not correlated with species richness and is distinctly higher in the Neotropical (164 genera); genus richness is similar in the Palaearctic, Nearctic and Australasian regions (128–131 genera) and is lower in the Afrotropical and Oriental regions with 110 and 94 genera, respectively. A mean number of about three genera per family occur in the Palaeartic, Nearctic and Oriental while an average of more than four genera characterizes the families of Australasian and Afrotropical regions and more than five genera those of the Neotropical. Australasian fauna is also characterized by the highest percentage of endemic genera (62%), followed by Neotropical (50.6%) and Afrotropical (47.2%) regions. Lower values are recorded for the Palaearctic (26.9%), Oriental (24.4%) and Nearctic (21.4%). The Palaearctic and Nearctic have the highest faunistic similarity, some minor affinities are also evident for the generic diversification of Holarctic and Oriental families. The faunas of Southern Hemisphere bioregions are more distinct and characterized by the presence of ancient Gondwanan clades with a regional diversification particularly evident in the Neotropics and Australasia. This scenario of water mite diversity and distribution reflect the basic vicariance pattern, isolation, phylogenetic diversification, recent climatic vicissitudes and episodes of dispersal between adjacent land masses together with extant ecological factors can be evoked to explain distribution patterns at a global scale. Guest editors: E. V. Balian, C. Lévêque, H. Segers & K. Martens Freshwater Animal Diversity Assessment     

Crystal structure of the non-regulatory A(4 )isoform of spinach chloroplast glyceraldehyde-3-phosphate dehydrogenase complexed with NADP

Here, we report the first crystal structure of a photosynthetic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) complexed with NADP. The enzyme, purified from spinach chloroplasts, is constituted of a single type of subunit (A) arranged in homotetramers. It shows non-regulated NADP-dependent and NAD-dependent activities, with a preference for NADP. The structure has been solved to 3.0 A resolution by molecular replacement. The crystals belong to space group C222 with three monomers in the asymmetric unit. One of the three monomers generates a tetramer using the space group 222 point symmetry and a very similar tetramer is generated by the other two monomers, related by a non-crystallographic symmetry, using a crystallographic 2-fold axis.The protein reveals a large structural homology with known GAPDHs both in the cofactor-binding domain and in regions of the catalytic domain. Like all other GAPDHs investigated so far, the A(4)-GAPDH belongs to the Rossmann fold family of dehydrogenases. However, unlike most dehydrogenases of this family, the adenosine 2'-phosphate group of NADP does not form a salt-bridge with any positively charged residue in its surroundings, being instead set in place by hydrogen bonds with a threonine residue belonging to the Rossmann fold and a serine residue located in the S-loop of a symmetry-related monomer. While increasing our knowledge of an important photosynthetic enzyme, these results contribute to a general understanding of NADP versus NAD recognition in pyridine nucleotide-dependent enzymes.Although the overall structure of A(4)-GAPDH is similar to that of the cytosolic GAPDH from bacteria and eukaryotes, the chloroplast tetramer is peculiar, in that it can actually be considered a dimer of dimers, since monomers are bound in pairs by a disulphide bridge formed across Cys200 residues. This bridge is not found in other cytosolic or chloroplast GAPDHs from animals, bacteria, or plants other than spinach.     

A study of iodothyronine 5'-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues

The present study was undertaken to investigate the peripheral iodothyronine 5'-monodeiodination in different human and rat tissues. We studied iodothyronine 5'-monodeiodinase type I (5'-DI) activity in liver, kidney, intestine, right cardiac atrium and skeletal muscle and we compared the results with those in rat tissues. Lodothyronine 5'- monodeiodinase type II (5'-DII) activity was studied in normal and ischemic human heart and in rat normal myocardium and brain. The 5'-DI activity (fmol/min x mg protein) in liver and kidney was significantly higher (p < 0.001, ANOVA) in normal rat tissue than in human. However, no significant differences were observed in 5'-DI activity between normal and tumoral human intestine or between intestinal tissue of man and rat. 5'-DI activity in normal human skeletal muscle was significantly higher than that in rat skeletal muscle (p < 0.05). The 5'-DI activity was lower in human ischemic myocardium when compared to normal myocardium either in humans (p < 0.05) or rat (p < 0.001). The Km of 5'-DI was significantly lower in rat than in human kidney and liver (p < 0.05). We conclude that 1) 5'-DI is distributed widely among extrathyroidal human and rat tissues and 5'-DII activity is detectable both in human and rat heart; 2) 5'-DI activity in liver and kidney is lower in man than in rat; 3) 5'-DI activity in the skeletal muscle is higher in man than in the rat; 4) 5'-DI activity is decreased in tumoral tissues of human liver and kidney and in ischemic myocardium, while no significant difference was found between human and rat cardiac 5'-DII activity.     

Comparative performance of the Mbita trap, CDC light trap and the human landing catch in the sampling of Anopheles arabiensis, An. funestus and culicine species in a rice irrigation in western Kenya

Background

IL-1β and IL-1RA levels are higher in the serum of cerebral malaria patients than in patients with mild malaria. Recently, the level of IL1B expression was reported to be influenced by a polymorphism in the promoter of IL1, IL1B -31C>T.

Methods

To examine whether polymorphisms in IL1B and IL1RA influence the susceptibility to cerebral malaria, IL1B -31C>T, IL1B 3953C>T, and IL1RA variable number of tandem repeat (VNTR) were analysed in 312 Thai patients with malaria (109 cerebral malaria and 203 mild malaria patients).

Results

In this population, IL1B -31C>T and IL1RA VNTRwere detected, while IL1B 3953C>T (i.e., IL1B 3953T) was not observed in the polymorphism screening for 32 patients. Further analyses for IL1B -31C>T and IL1RA VNTR in 110 cerebral malaria and 206 mild malaria patients showed no significant association of these polymorphisms with cerebral malaria.

Conclusion

The present results suggest that IL1B -31C>T and IL1RA VNTR polymorphisms do not play a crucial role in susceptibility or resistance to cerebral malaria.     

Advantages of larval control for African malaria vectors: Low mobility and behavioural responsiveness of immature mosquito stages allow high effective coverage

Background  

Based on sensitivity analysis of the MacDonald-Ross model, it has long been argued that the best way to reduce malaria transmission is to target adult female mosquitoes with insecticides that can reduce the longevity and human-feeding frequency of vectors. However, these analyses have ignored a fundamental biological difference between mosquito adults and the immature stages that precede them: adults are highly mobile flying insects that can readily detect and avoid many intervention measures whereas mosquito eggs, larvae and pupae are confined within relatively small aquatic habitats and cannot readily escape control measures.