Phylogeny, evolution and biogeography of the Quadrifoliovariinae Yamaguti, 1965 (Digenea : Lecithasteridae)

The Quadrifoliovariinae is revised and three new species of Quadrifoliovarium Yamaguit, 1965 from acanthurid fishes of the genus Naso from waters of the Indo-Pacific are described: Q, maceria n. sp. from N. tonganus, N. annulatus, N. fageni and N. brevirostris; Q. simplex n. sp. from N. tonganus and N. quannulatus; and Q. quattuordecim n. sp. from N. tonganus. Amendments are made to the characterisation of the Quadrifoliovariinae, Quadrifoliovarium, Bilacinia Manter, 1969 and Unilacinia Manter, 1969 in light of observations on type and new material. A molecular phylogeny based on ITS2 and 28S regions of the ribosomal DNA is proposed. The phylogeny suggests that U. asymmetrica is the most basal taxon and Q. simplex n. sp. and Q. quattuordecim n. sp. the most derived. Evolution of morphological traits within the Quadrifoliovariinae are discussed in light of the molecular phylogeny. Molecular sequences of the ITS2 rDNA were identical between specimens of Q. pritchardae collected off Exmouth (Indian Ocean), Heron Island and Lizard Island (Western Pacific) and Moorea (far Eastern Indo-Pacific), indicating a broad Indo-Pacific distribution. All members of the subfamily are recorded only from the acanthurid genus Naso, with the exception of B. lobatum (Yamaguti, 1970), which has been recorded from a pomacanthid. The restricted host range of the group is discussed in the light of the phylogeny of the host genus Naso.

Diagnostics of A Range of Highly Superorbital Carbon Dioxide Flows

Expansion tubes are impulse facilities capable of generating highly energetic hyper-sonic flows. This work surveys a broad range of flow conditions produced in the facility X1 with carbon dioxide test gas, for simulation of spacecraft entry into the Martian atmosphere. Conditions with nominal flow speeds of 7, 9, 11 and 13 km/s were tested. The freestream conditions were calibrated using static/Pitot pressure measurements and advanced optical diagnostics. An extensive set of holographic interferometry experiments was performed on flows over wedges for quantitative study of freestream and post-shock densities, and post-shock ionisation. A one-dimensional code with frozen and equilibrium chemistry capabilities was used to estimate the freestream conditions. An equilibrium chemistry model produced a good match to measured freestream quantities at the high enthalpy conditions which are a major aim of this facility's operation. The freestream in the lower enthalpy conditions was found to be heavily influenced by chemical non-equilibrium. Non-equilibrium in the final unsteady expansion process of flow generation was accounted for by switching from equilibrium to frozen chemistry at a predetermined point. Comparison between the freestream density results of holographic interferometry, pressure measurements and computations shows good agreement.

Wolbachia replication and host cell division in Aedes albopictus

Wolbachia pipientis is an obligate intracellular endosymbiont of a range of arthropod species. The microbe is best known for its manipulations of host reproduction that include inducing cytoplasmic incompatibility, parthenogenesis, feminization, and male-killing. Like other vertically transmitted intracellular symbionts, Wolbachiarsquos replication rate must not outpace that of its host cells if it is to remain benign. The mosquito Aedes albopictus is naturally infected both singly and doubly with different strains of Wolbachia pipientis. During diapause in mosquito eggs, no host cell division is believed to occur. Further development is triggered only by subsequent exposure of the egg to water. This study uses diapause in Wolbachia-infected Aedes albopictus eggs to determine whether symbiont replication slows or stops when host cell division ceases or whether it continues at a low but constant rate. We have shown that Wolbachia densities in eggs are greatest during embryonation and then decline throughout diapause, suggesting that Wolbachia replication is dependent on host cell replication.

Emission and holographic interferometry measurements in a superorbital expansion tube

Free-piston-driven expansion tubes are capable of generating flaw conditions over a wide range of enthalpies ranging from orbital up to superorbital velocities. Initial optical measurements aimed at investigating the flow in such a facility are presented. Emission studies were used to identify impurities in the how and to investigate spectral regions that are accessible by optical techniques. At moderate enthalpies, it was found that significant radiation resulted from metallic contaminants. At high enthalpies, the spectrum consisted of a number of atomic lines together with a broadband background component indicative of the presence of electrons. The presence of this radiation may limit the applicability of optical techniques that require spectral regions free from the influence of atomic transitions or background radiation. Emission spectroscopy (through Stark broadened hydrogen lines) and two-wavelength holographic interferometry were used to measure the electron number density behind a bow shock on a blunt body at conditions where significant ionization was observed. They yielded average concentrations of (3 +/- 1) x 10(17) cm(-3) from the emission measurements and (3.8 +/- 0.6) x 10(17) cm(-3) from the interferometry.

Potential strategies utilised by papillomavirus to evade host immunity

The co-evolution of papillomaviruses (PV) and their mammalian hosts has produced mechanisms by which PV might avoid specific and non-specific host immune responses. Low level expression of PV proteins in infected basal epithelial cells, together with an absence of inflammation and of virus-induced cell lysis, restricts the opportunity for effective PV protein presentation to immunocytes by dendritic cells. Additionally, PV early proteins, by a range of mechanisms, may restrict the efficacy of antigen presentation by these cells. Should an immune response be induced to PV antigens, resting keratinocytes (KC) appear resistant to interferon-gamma-enhanced mechanisms of cytotoxic T-lymphocyte (CTL)-mediated lysis, and expression of PV antigens by resting KC can tolerise PV-specific CTL. Thus, KC, in the absence of inflammation, may represent an immunologically privileged site for PV infection. Together, these mechanisms play a parr in allowing persistence of PV-induced proliferative skin lesions for months to years, even in immunocompetent hosts.

Role of chemical cues from cotton in mediating host selection and oviposition behaviour in Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae)

We investigated the role of chemoreception in the host selection and oviposition behaviour of Helicoverpa armigera in the laboratory using five cotton genotypes and synthetic volatile terpenes. Female moths oviposited on substrates treated with methanol, ethanol, acetone and pentane extracts of leaves, squares and flowers of the cotton genotypes. Phytochemicals soluble in pentane were the most efficient in eliciting oviposition behaviour. In a two-way bioassay, pentane extracts of leaves or squares of a Multiple Host-plant Resistance genotype (MHR11), Deltapine commercial (DP90), and Smith Red Leaf (SRL) received significantly more eggs than solvent-treated controls. Extracts of squares of the native genotype Gossypium nelsonii did not receive more eggs. Females preferred DP90 and MHR11 to SRL and G. nelsonii. Female moths also laid more eggs on pentane extracts of MHR11 flowers than MHR11 leaves from preflowering, early flowering and peak-flowering plants. In a flight chamber, female moths used olfactory cues at short range to mediate oviposition and discrimination between host plants. Egg-laying, mated females were attracted at a distance (1.5 m) to volatile compounds released by whole plants and odours emanating from filter papers treated with synthetic volatile terpenes. Individually, the terpenes did not stimulate any significant oviposition response. However, there was a significant oviposition response to a mixture of equal volumes of the terpenes (trans-beta-caryophyllene, alpha-pinene, beta-pinene, myrcene, beta-bisabolol, and alpha-humulene). Conversely, antennectomised (moths with transected antennae), egg-laying, mated females did not stimulate any significant oviposition response. The significance of these findings in relation to H. armigera hostplant selection are discussed.

Is there an association between normal cognitive functioning and trinucleotide repeat expansion at loci involved in neurodegenerative disorders?

Recent reports have shown neurodegenerative disorders to be associated with abnormal expansions of a CAG trinucleotide repeat allele at various autosomal loci. While normal chromosomes have 14 to 44 repeats, disease chromosomes may have 60 to 84 repeats. The number of CAG repeats on mutant chromosomes correlates with increasing severity of disease or decreasing age at onset of symptoms. Since we are interested in identifying the many quantitative trait loci (QTL) influencing brain functioning, we examined the possibility that the number of CAG repeats in the normal size range at these loci are relevant to "normal" neural functioning. We have used 150 pairs of adolescent (aged 16 years) twins and their parents to examine allele size at the MJD, SCA1, and DRPLA loci in heterozygous normal individuals. These are part of a large ongoing project using cognitive and physiological measures to investigate the genetie influences on cognition, and an extensive protocol of tests is employed to assess some of the key components of intellectual functioning. This study selected to examine full-scale psychometric IQ (FSIQ) and a measure of information processing (choice reaction time) and working memory (slow wave amplitude). CAG repeat size was determined on an ABI Genescan system following multiplex PCR amplification. Quantitative genetic analyses were performed to determine QTL effects of MJD, SCA1, and DRPLA on cognitive functioning. Analyses are in progress and will be discussed.

Extraordinary and extensive karyotypic variation: A 48-fold range in chromosome number in the gall-inducing scale insect Apiomorpha (Hemiptera : Coccoidea : Eriococcidae)

Chromosome number reflects strong constraints on karyotype evolution, unescaped by the majority of animal taxa. Although there is commonly chromosomal polymorphism among closely related taxa, very large differences in chromosome number are rare. This study reports one of the most extensive chromosomal ranges yet reported for an animal genus. Apiomorpha Rubsaamen (Hemiptera: Coccoidea: Eriococcidae), an endemic Australian gall-inducing scale insect genus, exhibits an extraordinary 48-fold variation in chromosome number with diploid numbers ranging from 4 to about 192. Diploid complements of all other eriococcids examined to date range only from 6 to 28. Closely related species of Apiomorpha usually have very different karyotypes, to the extent that the variation within some species- groups is as great as that across the entire genus. There is extensive chromosomal variation among populations within 17 of the morphologically defined species of Apiomorpha indicating the existence of cryptic species-complexes. The extent and pattern of karyotypic variation suggests rapid chromosomal evolution via fissions and (or) fusions. It is hypothesized that chromosomal rearrangements in Apiomorpha species may be associated with these insects' tracking the radiation of their speciose host genus, Eucalyptus.

C-reactive protein levels and the expansion of screen-detected abdominal aortic aneurysms in men

Background-C- reactive protein (CRP) levels have been shown to predict a number of cardiovascular outcomes. CRP levels have also been found to be elevated in patients with abdominal aortic aneurysms (AAAs). The aim of this study was to assess the relation between CRP levels and rates of expansion of small AAAs. Methods and Results-A cohort of men with small aneurysms was identified in a trial of screening with ultrasound scanning. After initial screening, men were rescanned at 6- to 12-month intervals. CRP levels were measured at the first follow-up visit. Rates of expansion and risk factors for expansion were assessed with the use of data from 545 men who attended for at least 1 scan after CRP levels were measured. These men were followed for a median of 48 (range, 5 to 69) months. The mean annual rate of expansion was 1.6 mm. The median CRP level was 2.6 mg/L in men with the smaller AAAs (30 to 39 mm, n=433) compared with 3.5 mg/L in men with larger AAAs (40 to 54 mm, n=112) (P=0.007). The multivariate age-adjusted logistic model confirmed initial aortic diameter to be the only factor associated with rapid expansion with an odds ratio of 7.2 (95% CI, 4.3,12.2) for an initial diameter of 40 to 54 mm relative to one of 30 to 39 mm. Conclusions-Most small aneurysms expand slowly. CRP levels are elevated in larger aneurysms but do not appear to be associated with rapid expansion. The most useful predictor of aneurysmal expansion in men is aortic diameter.

IL-1 beta breaks tolerance through expansion of CD25(+) effector T cells

IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn's disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1 beta drives proliferation and cytokine production by CD4(+)CD25(+)FoxP3(-) effector/memory T cells, attenuates CD4(+)CD25(+)FoxP3(+) regulatory T cell function, and allows escape of CD4(+)CD25(-) autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1 beta in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self.

The evolution of controlled multitasked gene networks: The role of introns and other noncoding RNAs in the development of complex organisms

Eukaryotic phenotypic diversity arises from multitasking of a core proteome of limited size. Multitasking is routine in computers, as well as in other sophisticated information systems, and requires multiple inputs and outputs to control and integrate network activity. Higher eukaryotes have a mosaic gene structure with a dual output, mRNA (protein-coding) sequences and introns, which are released from the pre-mRNA by posttranscriptional processing. Introns have been enormously successful as a class of sequences and comprise up to 95% of the primary transcripts of protein-coding genes in mammals. In addition, many other transcripts (perhaps more than half) do not encode proteins at all, but appear both to be developmentally regulated and to have genetic function. We suggest that these RNAs (eRNAs) have evolved to function as endogenous network control molecules which enable direct gene-gene communication and multitasking of eukaryotic genomes. Analysis of a range of complex genetic phenomena in which RNA is involved or implicated, including co-suppression, transgene silencing, RNA interference, imprinting, methylation, and transvection, suggests that a higher-order regulatory system based on RNA signals operates in the higher eukaryotes and involves chromatin remodeling as well as other RNA-DNA, RNA-RNA, and RNA-protein interactions. The evolution of densely connected gene networks would be expected to result in a relatively stable core proteome due to the multiple reuse of components, implying,that cellular differentiation and phenotypic variation in the higher eukaryotes results primarily from variation in the control architecture. Thus, network integration and multitasking using trans-acting RNA molecules produced in parallel with protein-coding sequences may underpin both the evolution of developmentally sophisticated multicellular organisms and the rapid expansion of phenotypic complexity into uncontested environments such as those initiated in the Cambrian radiation and those seen after major extinction events.

Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis

We report our experience with the combination of anti-thymocyte globulin (ATGAM) and tacrolimus in the treatment of 20 patients with steroid refractory and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GVHD prophylaxis. Thirteen patients developed a maximum of grade TV, five grade III and two grade II acute GVHD, with 15 patients being refractory to steroids and five dependent on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus (0.025-0.1 mg/kg/d) in addition to continuation of their high-dose steroids and cessation of their cyclosporine. Within 28 d of treatment, we observed eight complete responses (CR), six partial responses (PR) and six with no response. Overall response (CR + PR) was predicted by GVHD severity. Infectious complications occurred in 80% of patients. The median survival was 86.5 d (range, 21-1081 d) with 35% of patients remaining alive, Survival following combination therapy was significantly more likely in men (P < 0.001), skin-only GVHD (P = 0.027), less severe GVHD (P = 0.048), and in responders to tacrolimus and ATGAM (P< 0.001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a promising therapeutic combination for GVHD refractory to steroids and cyclosporine.

Cleavage of hemoglobin by hookworm cathespin D aspartic proteases and its potential contribution to host specificity

Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully feed, develop, and reproduce. To investigate the effects of host-parasite coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned and expressed aspartic proteases from canine and human hookworms. We show here that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum (Ac-APR-1) and the orthologous protease from the human hookworm Necator americanus (Na-APR-1) are expressed in the gut and probably exert their proteolytic activity extracellularly. Both proteases were detected immunologically and enzymatically in somatic extracts of adult worms. The two proteases were expressed in baculovirus, and both cleaved human and dog hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host between twofold (whole molecule) and sixfold (synthetic peptides) more efficiently than Hb from the nonpermissive host, despite the two proteases' having identical residues lining their active site clefts. Furthermore, both proteases cleaved Hb at numerous distinct sites and showed different substrate preferences. The findings suggest that the paradigm of matching the molecular structure of the food source within a host to the molecular structure of the catabolic proteases of the parasite is an important contributing factor for host-parasite compatibility and host species range.

DNA sequence variation in the ITS-1 rDNA subunit and host relationships in sorghum midge, Stenodiplosis sorghicola (Coquillett) (Diptera : Cecidomyiidae), in Australia

Sequence variation in the internal transcribed spacer (ITS-1) ribosomal DNA subunit was examined for sorghum midge obtained from introduced and native hosts in south-eastern and central Queensland. No variation was observed relative to host plant or geographical distance for midges collected from two introduced hosts, grain sorghum (Sorghum bicolor ) and Johnson grass (S. halepense ); however, sequence differences were observed between midges from introduced and native hosts and among midges from a single native host, slender bluegrass (Dichanthium affine ). No evidence was observed of introduced midges on native hosts, or vice versa. These results agree with previously hypothesised host distributions for native and introduced midges in Australia, and expand the sample of introduced hosts to include Johnson grass. They suggest that Stenodiplosis sorghicola , the principal midge infesting grain sorghum, is also the most common species on Johnson grass. This confirms that Johnson grass plays a role in the population dynamics of S. sorghicola and suggests that midges originating from Johnson grass may influence levels of infestation in grain sorghum.