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.     

Multiple mating strategies explain unexpected genetic mixing of New Zealand fur seals with two congenerics in a recently recolonized population

Human impacts on natural systems can cause local population extinctions, which may promote redistribution of taxa and secondary contact between divergent lineages. In mammalian populations that have mating systems shaped by polygyny and sexual selection, the potential for hybridization to ensue and persist depends on individual and demographic factors. At Macquarie Island, a recently formed fur seal population is comprised of both sexes of breeding Antarctic (Arctocephalus gazella) and subantarctic (A. tropicalis) fur seals, and an itinerant collection of male New Zealand fur seals (A. forsteri), presumed to be non-breeders due to their absence from principle breeding areas. The mating system of the three species is described as resource-defence polygyny: males defend beach territories containing breeding females for exclusive mating rights. A recent genetic study identified a high level of hybridization in the population (17-30%), unexpectedly involving all three species. This study examined the source of involvement in breeding by A. forsteri with respect to mating strategies operating in the population. Ninety-five (10%) pups born from 1992 to 2003 were genetically identified as New Zealand hybrids. Most resulted from reproduction within territories by New Zealand hybrids of both sexes, although some were conceived extra-territorially, indicating that males successfully utilize strategies other than territory holding to achieve paternities. Female reproductive status influenced mating partner and mating location, and females without pups were more likely to conceive extra-territorially and with A. forsteri males. This study illustrates an important consequence of low heterospecific discrimination in a sympatric population of long-lived mammals.     

Induced hyperlipaemia and immune challenge in locusts

Injections of immunogens, such as beta-1,3-glucan or lipopolysaccharide (LPS), bring about a marked hyperlipaemia with associated changes in lipophorins and apolipophorin-III in the haemolymph of Locusta migratoria. These changes are similar to those observed after injection of adipokinetic hormone (AKH). The possibility that endogenous AKH is released as part of the response to these immunogens is investigated using passive immunisation against AKH-I, and measurement of AKH-I titre in the haemolymph after injection of immunogens. The data presented show that, despite the similarity of the changes brought about by the presence of immunogens in the haemolymph to those brought about by AKH, there is no release of endogenous AKH after injection of laminarin or LPS. A direct effect of the immunogens on release of neutral lipids by the fat body cannot be demonstrated in vitro, and the mechanism by which hyperlipaemia is induced during immune challenge remains uncertain.     

The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids

GPR41 and GPR43 are related members of a homologous family of orphan G protein-coupled receptors that are tandemly encoded at a single chromosomal locus in both humans and mice. We identified the acetate anion as an agonist of human GPR43 during routine ligand bank screening in yeast. This activity was confirmed after transient transfection of GPR43 into mammalian cells using Ca(2+) mobilization and [(35)S]guanosine 5'-O-(3-thiotriphosphate) binding assays and by coexpression with GIRK G protein-regulated potassium channels in Xenopus laevis oocytes. Other short chain carboxylic acid anions such as formate, propionate, butyrate, and pentanoate also had agonist activity. GPR41 is related to GPR43 (52% similarity; 43% identity) and was activated by similar ligands but with differing specificity for carbon chain length, with pentanoate being the most potent agonist. A third family member, GPR42, is most likely a recent gene duplication of GPR41 and may be a pseudogene. GPR41 was expressed primarily in adipose tissue, whereas the highest levels of GPR43 were found in immune cells. The identity of the cognate physiological ligands for these receptors is not clear, although propionate is known to occur in vivo at high concentrations under certain pathophysiological conditions.     

A comparison of scholastic and collegiate longsnapping techniques

The purpose of this study was to identify the differences that exist between collegiate (CS) and scholastic (SS) longsnappers. Six CS (21.4 +/- 1.37 years) and 7 SS (16.7 +/- 1.11 years) longsnappers were filmed performing 10 longsnaps each. The CS and SS longsnappers had 7.0 +/- 0.89 and 2.7 +/- 0.95 years experience longsnapping, respectively. Each of the 10 longsnaps for all subjects were analyzed for takeoff velocity and accuracy. The snap that most closely approximated the individual snapper's median values for takeoff velocity and accuracy was digitized using a 20-point model. CS were both faster (0.85 +/- 0.10 seconds vs. 1.25 +/- 0.19 seconds) and more accurate in terms of mean radial error (29.36 +/- 8.4 cm vs. 47.2 +/- 8.26 cm) than their SS counterparts. These differences were related to body positioning both before and during the longsnap. CS exhibited more shoulder flexion (135 +/- 6.33 degrees ; vs. 98 +/- 9.01 degrees ) and greater elbow extension (133 +/- 8.1 degrees vs. 95 +/- 6.77 degrees ) in the set position phase, along with greater center of mass movement (0.27 +/- 0.02 m vs. 0.14 +/- 0.04 m) in the anterior-posterior direction and less hip flexion (72 +/- 1.85 degrees vs. 49 +/- 9.42 degrees ) during the preflight phase. Longsnapping experience and accuracy were significantly related (r = -0.82, p < 0.05). These results suggest that body positioning both before and during the longsnap motion significantly influence the velocity and accuracy of the longsnap.     

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.     

Isolation, characterization and biological activity of a CRF-related diuretic peptide from Periplaneta americana L.

A diuretic peptide (Periplaneta-DP) has been isolated from extracts of whole heads of the cockroach, Periplaneta americana. The purified peptide increases cyclic AMP production and the rate of fluid secretion by isolated Malpighian tubules in vitro. In the fluid secretion assay, the response to native Periplaneta-DP is comparable to that obtained with crude extracts of cockroach corpora cardiaca, and the EC50 lies between 10(-8) and 10(-9) M. The primary structure of Periplaneta-DP was established as a 46-residue amidated peptide: T G S G P S L S I V N P L D V L R Q R L L L E I A R R R M R Q S Q D Q I Q A N R E I L Q T I-NH2. Periplaneta-DP is a further member of the recently established family of CRF-related insect diuretic peptides.