Syk-Dependent Cytokine Induction by Dectin-1 Reveals a Novel Pattern Recognition Pathway for C Type Lectins

Pattern-recognition receptors (PRRs) detect molecular signatures of microbes and initiate immune responses to infection. Prototypical PRRs such as Toll-like receptors (TLRs) signal via a conserved pathway to induce innate response genes. In contrast, the signaling pathways engaged by other classes of putative PRRs remain ill defined. Here, we demonstrate that the β-glucan receptor Dectin-1, a yeast binding C type lectin known to synergize with TLR2 to induce TNFα and IL-12, can also promote synthesis of IL-2 and IL-10 through phosphorylation of the membrane proximal tyrosine in the cytoplasmic domain and recruitment of Syk kinase. syk−/− dendritic cells (DCs) do not make IL-10 or IL-2 upon yeast stimulation but produce IL-12, indicating that the Dectin-1/Syk and Dectin-1/TLR2 pathways can operate independently. These results identify a novel signaling pathway involved in pattern recognition by C type lectins and suggest a potential role for Syk kinase in regulation of innate immunity.

Saturated salt solutions for humidity control and the survival of dry powder and oil formulations of Beauveria bassiana conidia

Oil-based formulated conidia sprayed on steel plates and conidia powder (control) of Beauveria bassiana isolate IMI 386243 were stored at temperatures from 10 to 40 degrees C in desiccators over saturated salt solutions providing relative humidities from 32 to 88%, or in hermetic storage at 40 degrees C, and moisture contents in equilibrium with 33 or 77% relative humidity. The negative semi-logarithmic relation (P < 0.005) between conidia longevity (at 40 degrees C) and equilibrium relative humidity did not differ (P > 0.25) between formulated conidia and conidia powder. Despite this, certain saturated salts provided consistently greater longevity (NaCl) and others consistently shorter longevity (KCl) for formulated conidia compared to conidia powder. These results, analysis of previous data, and comparison with hermetic storage, indicate that storage of conidia over saturated salt solutions provides inconsistent responses to environment and so may be problematic for bio-pesticide research. In hermetic storage, oil formulation was not deleterious to longevity and in the more moist environment enhanced survival periods. (c) 2005 Elsevier Inc. All rights reserved.

Consumer welfare effects of introducing and labeling genetically modified food

Non-hypothetical valuations obtained from experimental auctions in three United States and two European locations were used to calculate welfare effects of introducing and labeling of genetically modified food. Under certain assumptions, we find that introduction of genetically modified food has been welfare enhancing, on average, for United States consumers but not so for Europeans and while mandatory labeling has been beneficial for European consumers, such a policy would be detrimental in the United States. (c) 2005 Elsevier B.V. All rights reserved.

Grazing management of calcareous grasslands and its implications for the conservation of beetle communities

Calcareous grasslands are an important habitat for floral and faunal communities in the UK and Europe. Declines due to changes in management, scrub invasion and agricultural improvement have left much of the remnants of this habitat in a degraded and fragmented state. Grazing, by cattle or sheep, is one of the main management practices used to maintain and improve the floral and faunal quality of calcareous grassland. The long-term impacts of different grazing regimes, however, are poorly understood, particularly in terms of the invertebrate communities. This study contrasted the impacts of recently introduced and long-term sheep or cattle grazing on beetle communities present on one of the largest areas of calcareous grassland in Europe, the Salisbury Plain military training Area, UK. No effects of grazing management on beetle abundance, species. richness or evenness were found, but plant diversity and overall percentage cover of grasses did influence beetle diversity. Proportions of the total number of individuals and overall species richness within beetle guilds (predatory, phytophagous, flower/seed feeders, root feeders and foliage feeders) were strongly influenced by both the duration and type of grazing animal. At the species level, beetle community structure showed significant differences between ungrazed, long-term cattle and long-term sheep grazing treatments. Changes in plant community structure were found to influence beetle community structure. The significance of these results is discussed in terms of the long-term impacts of grazing on beetle community structure, and the benefits of different grazing regimes for the conservation management of calcareous grasslands. (c) 2005 Elsevier Ltd. All rights reserved.

Induction of heme oxygenase 1 by moderately oxidized low-density lipoproteins in human vascular smooth muscle cells: role of mitogen-activated protein kinases and Nrf2

Oxidized low-density lipoproteins (LDL) play a central role in atherogenesis and induce expression of the antioxidant stress protein heme oxygenase 1 (HO-1). In the present study we investigated induction of HO-1 and adaptive increases in reduced glutathione (GSH) in human aortic smooth muscle cells (SMC) in response to moderately oxidized LDL (moxLDL, 100 mu g protein/ml, 24 h), a species containing high levels of lipid hydroperoxides. Expression and activity of HO-1 and GSH levels were elevated to a greater extent by moxLDL than highly oxidized LDL but unaffected by native or acetylated LDL. Inhibitors of protein kinase C (PKC) or mitogen-activated protein kinases (MAPK) p38(MAPK) and MEK or c-jun-NH2-terminal kinase (JNK) significantly attenuated induction of HO-1. Phosphorylation of p38(MAPK), extracellular signal-regulated kinase (ERK1/2), or JNK and nuclear translocation of the transcription factor Nrf2 were enhanced following acute exposure of SMC to rnoxLDL (100 mu g proteiri/ml, 1-2 h). Pretreatment of SMC with the antioxidant vitamin C (100 mu M, 24 h) attenuated the induction of HO-1 by moxLDL. Native and oxidized LDL did not alter basal levels of intracellular ATP, mitochondrial dehydrogenase activity, or expression of the lectin-like oxidized LDL receptor (LOX-1) in SMC. These findings demonstrate for the first time that activation of PKC, p38(MAPK), JNK, ERK1/2, and Nrf2 by oxidized LDL in human SMC leads to HO-1 induction, constituting an adaptive response against oxidative injury that can be ameliorated by vitamin C. (C) 2005 Elsevier Inc. All rights reserved.

Genotypic and phenotypic diversity of a baculovirus population within an individual insect host

It is becoming increasingly apparent that many pathogen populations, including those of insects, show high levels of genotypic variation. Baculoviruses are known to be highly variable, with isolates collected from the same species in different geographical locations frequently showing genetic variation and differences in their biology. More recent Studies at smaller scales have also shown that virus DNA profiles from individual larvae can show polymorphisms within and between populations of the same species. Here, we investigate the genotypic and phenotypic variation of an insect baculovirus infection within a single insect host. Twenty four genotypically distinct nucleopolyhedrovirus (NPV) variants were isolated from an individual pine beauty moth, Panolis flammea, caterpillar by in vivo cloning techniques. No variant appeared to be dominant in the population. The Pafl NPV variants have been mapped using three restriction endonucleases and shown to contain three hypervariable regions containing insertions of 70-750 bp. Comparison of seven of these variants in an alternative host, Mamestra brassicae, demonstrated that the variants differed significantly in both pathogenicity and speed of kill. The generation and maintenance of pathogen heterogeneity are discussed. (c) 2005 Elsevier Inc. All rights reserved.

New challenges in the study of the mammalian tachykinins

There is an expanding repertoire of mammalian tachykinins produced by a variety of tachykinin genes, gene splicing events and peptide processing. Novel tachykinin-binding molecules/receptors are proposed, but only, three tachykinin receptors are identified with certainty. The question remains - do more tachykinin receptors exist or is there just the need to reappraise Our understanding of the known receptors? The tachykinin NK1 receptor, the preferred receptor for both substance P and the peripheral SP-like endokinins, exists in several tissue-specific conformations and isoforms and may provide some clues. This review addresses recent advances in this exciting field and raises challenging new concepts. (c) 2005 Elsevier Inc. All rights reserved.

Supramolecular parallel beta-sheet and amyloid-like fibril forming peptides using delta-aminovaleric acid residue

Four terminally blocked tripeptides containing delta-aminovaleric acid residue self-assemble to form supramolecular beta-sheet structures as are revealed from their FT-IR data. Single crystal X-ray diffraction studies of two representative peptides also show that they form parallel beta-sheet structures. Self-aggregation of these beta-sheet forming peptides leads to the formation of fibrillar structures, as is evident from scanning electron microscopic (SEM) and transmission electron microscopic (TEM) images. These peptide fibrils bind to a physiological dye, Congo red and exhibit a typical green-gold birefringence under polarized light, showing close resemblance to neurodegenerative disease causing amyloid fibrils. (c) 2005 Elsevier Ltd. All rights reserved.

Can a consecutive double turn conformation be considered as a peptide based molecular scaffold for supramolecular helix in the solid state?

Helices and sheets are ubiquitous in nature. However, there are also some examples of self-assembling molecules forming supramolecular helices and sheets in unnatural systems. Unlike supramolecular sheets there are a very few examples of peptide sub-units that can be used to construct supramolecular helical architectures using the backbone hydrogen bonding functionalities of peptides. In this report we describe the design and synthesis of two single turn/bend forming peptides (Boc-Phe-Aib-Ile-OMe 1 and Boc-Ala-Leu-Aib-OMe 2) (Aib: alpha-aminoisobutyric acid) and a series of double-turn forming peptides (Boc-Phe-Aib-IIe-Aib-OMe 3, Boc-Leu-Aib-Gly-Aib-OMe 4 and Boc-gamma-Abu-Aib-Leu-Aib-OMe 5) (gamma-Abu: gamma-aminobutyric acid). It has been found that, in crystals, on self-assembly, single turn/bend forming peptides form either a supramolecular sheet (peptide 1) or a supramolecular helix (peptide 2). unlike self-associating double turn forming peptides, which have only the option of forming supramolecular helical assemblages. (c) 2005 Elsevier Ltd. All rights reserved.

Gas-solid reactions of single crystals: a study of reactions of NH3 and NO2 with single crystalline organic substrates by infrared microspectroscopy

Reaction of single crystals of benzoic and trans-cinnamic acids with 200 Torr pressure of ammonia gas in a sealed glass bulb at 20 degrees C generates the corresponding ammonium salts; there is no sign of any 1:2 adduct as has been reported previously for related systems. Isotopic substitution using ND3 has been used to aid identification of the products. Adipic acid likewise reacts with NH3 gas to form a product in which ammonium salts are formed at both carboxylic acid groups. Reaction of 0.5 Torr pressure of NO2 gas with single crystals of 9-methylanthracene and 9-anthracenemethanol in a flow system generates nitrated products where the nitro group appears to be attached at the 10-position, i.e. the position trans to the methyl or methoxy substituent on the central ring. Isotopic substitution using (NO2)-N-15 has been used to confirm the identity of the bands arising from the coordinated NO2 group. The products formed when single crystals of hydantoin are reacted with NO2 gas under similar conditions depend on the temperature of the reaction. At 20 degrees C, a nitrated product is formed, but at 65 degrees C this gives way to a product containing no nitro groups. The findings show the general applicability of infrared microspectroscopy to a study of gas-solid reactions of organic single crystals. (c) 2005 Elsevier B.V. All rights reserved.