The 5'-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation.

The role of the 5'-untranslated region (5'UTR) in the replication of enteroviruses has been studied by using a series of poliovirus type 3 (PV3) replicons containing the chloramphenicol acetyltransferase reporter gene in which the 5'UTR was replaced by the 5'UTR of either coxsackievirus B4 or human rhinovirus 14 or composite 5'UTRs derived from sequences of PV3, human rhinovirus 14, coxsackievirus B4, or encephalomyocarditis virus. The results indicate that efficient replication of an enterovirus genome requires a compatible interaction between the 5'-terminal cloverleaf structure and the coding and/or 3'-noncoding regions of the genome. A crucial determinant of this interaction is the stem-loop formed by nucleotides 46 to 81 (stem-loop d). The independence of the cloverleaf structure formed by the 5'-terminal 88 nucleotides and the ribosome landing pad or internal ribosome entry site (IRES) was investigated by constructing a 5'UTR composed of the PV3 cloverleaf and the IRES from encephalomyocarditis virus. Chloramphenicol acetyltransferase gene-containing replicons and viruses containing this recombinant 5'UTR showed levels of replication similar to those of the corresponding genomes containing the complete PV3 5'UTR, indicating that the cloverleaf and the IRES may be regarded as functionally independent and nonoverlapping elements.     

Pathways of soil genesis in the Coast Range of Oregon, USA

Background and Aims

Soil chronosequences on marine terraces along the Pacific Coast of California and Oregon show evidence of podzolization, though soils ultimately evolve to Ultisols. It is not clear if this pathway of soil evolution can be extended to the humid, inland Oregon Coast Range.

Methods

We analyzed soil properties for a fluvial terrace chronosequence sampled along the Siuslaw River (Oregon, USA) about 50 km from the Pacific coast. The seven terraces ranged in age from <3.5 ky to nearly 1,000 ky.

Results

There was no evidence of early podsolization. Instead, evidence was found that andisolization starts early and occurs even in older soils when pedogenic iron accumulation and clay synthesis and illuviation dominate. Soils develop the morphology characteristic of Ultisols sometime between 20 and 70 ky, but high levels of oxalate extractable iron and aluminum satisfy criteria of an andic subgroup. Alfisols are not formed as an intermediary stage.

Conclusions

The lack of Spodosols inland is due to the inland shift from udic to ustic or xeric moisture regime, which favors summer drying and ripening of short-range order minerals rather than deep leaching or translocation. Other factors are higher pH, different organic chemistry and faster calcium cycling under the Douglas fir inland when compared to the Sitka spruce of the coastal terraces.     

Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.     

Mhc haplotype H6 is associated with sustained control of SIVmac251 infection in Mauritian cynomolgus macaques

The restricted diversity of the major histocompatibility complex (MHC) of Mauritian cynomolgus macaques provides powerful opportunities for insight into host-viral interactions and cellular immune responses that restrict lentiviral infections. However, little is known about the effects of Mhc haplotypes on control of SIV in this species. Using microsatellite-based genotyping and allele-specific PCR, Mhc haplotypes were deduced for 35 macaques infected with the same stock of SIVmac251. Class I haplotype H6 was associated with a reduction in chronic phase viraemia (p = 0.0145) while a similar association was observed for H6 class II (p = 0.0063). An increase in chronic phase viraemia, albeit an insignificant trend, was observed in haplotype H5-positive animals. These results further emphasise the value of genetically defined populations of non-human primates in AIDS research and provide a foundation for detailed characterisation of MHC restricted cellular immune responses and the effects of host genetics on SIV replication in cynomolgus macaques. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations.     

Genetic and Biochemical Characterization of Nectria haematococca Strains with Adhesive and Adhesion-Reduced Macroconidia

A previous study reported the isolation of two mutants (LE1 and LE2) of the plant pathogenic fungus Nectria haematococca (anamorph, Fusarium solani f. sp. cucurbitae) with macroconidia with reduced ability to adhere (Att^-) to zucchini fruits and polystyrene. The adhesion-reduced-phenotype in LE1 and LE2 macroconidia is temperature sensitive and dependent on the concentration of nutrients. Classical genetic analysis of progeny derived from LE1 identified a mutation in a genetic locus, named Att1. The 90-kDa glycoprotein and macroconidial tip mucilage which were previously associated with the development of adhesion competence in Att⁺ macroconidia are specifically associated with macroconidia; neither is produced on microconidia, which are relatively nonadherent. However, macroconidia of both Att⁺ and Att^- strains produce the 90-kDa glycoprotein and the macroconidial tip mucilage.     

REPRODUCTIVE CONFLICT IN BUMBLEBEES AND THE EVOLUTION OF WORKER POLICING

Worker policing (mutual repression of reproduction) in the eusocial Hymenoptera represents a leading example of how coercion can facilitate cooperation. The occurrence of worker policing in “primitively” eusocial species with low mating frequencies, which lack relatedness differences conducive to policing, suggests that separate factors may underlie the origin and maintenance of worker policing. We tested this hypothesis by investigating conflict over male parentage in the primitively eusocial, monandrous bumblebee, Bombus terrestris. Using observations, experiments, and microsatellite genotyping, we found that: (a) worker‐ but not queen‐laid male eggs are nearly all eaten (by queens, reproductive, and nonreproductive workers) soon after being laid, so accounting for low observed frequencies of larval and adult worker‐produced males; (b) queen‐ and worker‐laid male eggs have equal viabilities; (c) workers discriminate between queen‐ and worker‐laid eggs using cues on eggs and egg cells that almost certainly originate from queens. The cooccurrence in B. terrestris of these three key elements of “classical” worker policing as found in the highly eusocial, polyandrous honeybees provides novel support for the hypothesis that worker policing can originate in the absence of relatedness differences maintaining it. Worker policing in B. terrestris almost certainly arose via reproductive competition among workers, that is, as “selfish” policing.     

A mouse model for poliovirus neurovirulence identifies mutations that attenuate the virus for humans.

A mutation in the genome of poliovirus type 3 that is known to reduce neurovirulence in humans similarly reduces neurovirulence in mice when incorporated into a mouse-adapted-human poliovirus recombinant. Viral recombinants with a uracil at nucleotide position 472 in the 5'-noncoding regions of their genomes are unable to replicate in the mouse brain. Viral recombinants with a cytosine at this position are neurovirulent in mice. Neurovirulence of poliovirus in mice may therefore prove to be a useful indicator of the genetic stability of new attenuating mutations created by site-directed mutagenesis.     

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

Background

Avoidance of allergens is still recommended as the first and best way to prevent allergic illnesses and their comorbid diseases. Despite a variety of attempts there has been very limited success in the area of environmental control of allergic disease. Our objective was to identify a non-invasive, non-pharmacological method to reduce indoor allergen loads in atopic persons' homes and public environments. We employed a novel in vivo approach to examine the possibility of using aluminum sulfate to control environmental allergens.

Methods

Fifty skin test reactive patients were simultaneously skin tested with conventional test materials and the actions of the protein/glycoprotein modifier, aluminum sulfate. Common allergens, dog, cat, dust mite, Alternaria, and cockroach were used in the study.

Results

Skin test reactivity was significantly reduced by the modifier aluminum sulfate. Our studies demonstrate that the effects of histamine were not affected by the presence of aluminum sulfate. In fact, skin test reactivity was reduced independent of whether aluminum sulfate was present in the allergen test material or removed prior to testing, indicating that the allergens had in some way been inactivated.

Conclusion

Aluminum sulfate was found to reduce the in vivo allergic reaction cascade induced by skin testing with common allergens. The exact mechanism is not clear but appears to involve the alteration of IgE-binding epitopes on the allergen. Our results indicate that it may be possible to diminish the allergenicity of an environment by application of the active agent aluminum sulfate, thus producing environmental control without complete removal of the allergen.