Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.

Stock splits: Implications for investor trading costs

Stock splits are known to have a negative effect on market quality—while stock prices adjust consistently with the split's scale, the bid/ask spread and market depth do not. Two possible explanations for the relative increase in spread are that (i) splits cause an increase in market maker costs that are passed along to investors or (ii) splits provide a mechanism for market makers to increase excess profits. Using a robust econometric methodology, we find evidence of the latter, which raises questions about the motivation of the splitting practice. We also document that while NASDAQ spreads appear to adjust more fully than those of NYSE/AMEX stocks, NASDAQ spreads are higher in general.

On the robustness of short-term interest rate models

This paper investigates the robustness of a range of short–term interest rate models. We examine the robustness of these models over different data sets, time periods, sampling frequencies, and estimation techniques. We examine a range of popular one–factor models that allow the conditional mean (drift) and conditional variance (diffusion) to be functions of the current short rate. We find that parameter estimates are highly sensitive to all of these factors in the eight countries that we examine. Since parameter estimates are not robust, these models should be used with caution in practice.

Dysarthria and dysphagia following treatment for a fourth ventricle choroid plexus papilloma

The present case report describes the presence of a persistent dysarthria and dysphagia as a consequence of surgical intervention for a choroid plexus papilloma (CPP). WM was a nine year ten month old male who at the time of the present study was seven years post-surgery. A comprehensive perceptual and instrumental test battery was used to document the nature of the dysarthria incorporating all components of speech production including respiration, phonation, resonance, articulation, and prosody. The nature of the dysphagia was evaluated through the use of videofluoroscopic evaluation of swallowing (VFS). Assessments confirmed the presence of a LMN dysarthria, marked by deficits in phonation, respiration, and prosody. Dysphagia assessment revealed deficits in oral preparatory, oral and pharyngeal stages of the swallow. The presence of persistent dysarthria and dysphagia in this case has a number of important implications for the management of children undergoing surgery for fourth ventricle CPPs, in particular the need for appropriate treatment, as well as counselling prior to surgery of the possible negative outcomes related to speech and swallowing. (C) 2003 Elsevier Science Ltd. All rights reserved.

The suitability of written education materials for stroke survivors and their carers

This study evaluated the suitability of written materials for stroke survivors and their carers. Twenty stroke survivors and 14 carers were interviewed about the stroke information they had received and their perceptions of the content and presentation of materials of increasing reading difficulty. The mean readability level of materials (grade 9) was higher than participants’ mean reading ability (grade 7–8). Satisfaction with materials decreased as the content became more difficult to read. Seventy-five percent reported that their information needs were not met in hospital. More stroke survivors with aphasia wanted support from health professionals to read and understand written information, and identified simple language, large font size, color, and diagrams to complement the text as being important features of written materials. Simple materials that meet clients’ information needs and design preferences may optimally inform them about stroke.

Pseudotrypanosoma elphinstonae sp n., a trichomonad symbiotic in Schedorhinotermes (Isoptera : Rhinotermitidae)

A new species of Pseudotrypanosoma, P. elphinstonae sp. n., is described which is symbiotic within the hindguts of the rhinotermitid termites Schedorhinotermes secundus and S. intermedius. P. elphinstonae possesses most of the features of the genus: 4 anterior flagella, prominent costa and recurrent flagellum forming an undulating membrane and simple bean-shaped parabasal body. The mastigont complex is of similar composition and arrangement to other trichomonads but the pelto-axostylar complex is greatly simplified being composed of a single layer of microtubules which do not over lap and cannot be distinguished into separate structures. The undulating membrane is much smaller than in related species; the costa is smaller and simpler and there are no microtubular bundles connecting it to the recurrent flagellum. Comparison of the ultrastructure of P. elphinstonae sp. n. with that of P. giganteum demonstrated that P. elphinstonae sp. n. in addition to being much smaller in size had a correspondingly simper ultrastructural organisation lacking several organelles which characterise the latter species.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Trichostome ciliates from Australian marsupials. III. Megavestibulum gen. nov. (Litostomatea : Macropodiniidae)

A new macropodiniid ciliate genus, Megavestibulum, is described which is endocommensal in the stomach of macropodid marsupials. Two new species, M. morganorum and M. kuhri, are described from Macropus dorsalis and Wallabia, bicolor respectively. Megavestibulum is holotrichous, the somatic ciliation arranged into meridional, curving kineties between broad ridges. The interkinetal ridges are lined apically by thick-walled vacuoles similar to those lining the longitudinal grooves of Macropodinium. The conical vestibulum is apical and very large, occupying up to 1/3 of the cell volume. The vestibular lip appears closable and has a cleft which may allow distention of the vestibullum to ingest large food items. The vestibular ultrastructure is similar to that of Macropodinium including the presence of vestibular vacuoles and the hemispherical differentiation of the distribution of small nematodesmata. Many specimens contained ingested whole ciliates of the genera Amylovorax and Polycosta. The structure of the vestibulum suggests that Megavestibulum is adapted for life as an active predator of other stomach ciliates as well as sweeping in small particulates. The morphology of Megavestibulum suggests that it represents the plesiomorphic body plan within the family Macropodiniidae.

Trichostome ciliates from Australian marsupials. I. Bandia gen nov (Litostomatea : Amylovoracidae)

A new genus of amylovoracid ciliates, Bandia gen.nov., is described. They are endosymbiotic/endocommensal in the stomachs of macropodid marsupials. Six new species, B. beveridgei, B. equimontanensis, B. tammar, B. deveneyi, B. cribbi and B. smalesae, are described from Setonix brachyurus, Petrogale assimilis, Macropus eugenii, M. robustus, M. parryi and M. agilis respectively. The gross morphology of Bandia is similar to that of Bitricha, with holotrichous somatic ciliation in two fields, longitudinal dorsal and oblique ventral. The somatic kineties are arranged in groups between non-ciliated. major interkinetal ridges; the groups of kineties thus give the cell a banded appearance. Several species are bimorphic, one form holotrichous and the other with a glabrous right body groove which appears to be derived from an ingrowth of one of the major interkinetal ridges. The groove may function in attachment either in sequestration or conjugation. The ultrastructure of the somatic kineties and the oral structures is similar to that of Amylovorax. Bandia also has unique ultrastructural features associated with the major interkinetal ridges, right body groove and a karyophore. Morphological evolution within the Amylovoracidae may have proceeded from simple forms such as Amylovorax via a process of cellular torsion and/or oral migration to forms similar to Bitricha and by further torsion and cellular elaboration to Bandia.

Trichostome ciliates from Australian marsupials. II. Polycosta gen. nov (Litostomatea : Polycostidae fam. nov.)

A new family, Polycostidae, containing one new genus, Polycosta, of ciliates endwocommensal in the stomachs of macropodid marsupials is described. Four new species, A roundi, P. turniae, A sebastopolensis and P. parma are described from Wallabia bicolor, Macropus dorsalis, Petrogale herberti and M. eugenii, respectively. Polycosta is holotrichous with slightly spiral meridional kineties arranged between broad interkinetal ridges. The ultrastructure of one representative species displays the knitted together pattern of postciliary microtubules and kinetodesmata of somatic kinetids common in trichostomes and the interkinetal ridges are dominated by layers of dark bodies but lack ectoplasmic hydrogenosomes. The vestibulum is conical and its aperture appears capable of closing tightly in most species; vesibular kineties are continuations of the right somatic kineties into the vestibulum. There is a prominent phago-plasm delimited internally by a basket of nematodesmata derived from electron dense plates at the bases of kinetosomes the anterior somatic and vestibular kineties. There is a prominent cytoproct which is situated within an invagination of the cell in some species. Polycosta is similar to Amylovorax in terms of gross morphology, somatic ciliature and cortical ultrastructure. The vestibular ultrastructure, however, is more similar to that of Macropodinium. The affinities of the group are thus not clear and this unique combination of characters supports the erection of a new family.

Trichostome ciliates from Australian marsupials. IV. Distribution of the ciliate fauna

Trichostome ciliates are associated with many different lineages of herbivorous mammals but there are few comparative studies of these associations in each lineage of herbivores. Here the occurrence of the ciliate fauna in a range of herbivorous marsupials (diprotodonts) is investigated and compared with that of ruminants. A total of 371 potential host animals, representing 33 species and 7 families, were examined for the presence of ciliates. The prevalence of endocommensal ciliates within individual host species varied between 0 and 100%. Of the different dietary groups of marsupials examined, only foregut (macropodids) and hindgut (vombatids) fermentative herbivores were found to harbour ciliates; carnivorous (dasyurids), omnivorous (peramelids) and midgut fermenting herbivores (phalangeroids) all lacked ciliates. The majority of ciliate species were oioxenic, several occurred in closely related hosts and some were able to colonise unnatural hosts in captive populations. Ciliate prevalences were found to vary at all levels: between hosts of different species, between conspecific hosts collected at different localities or seasons and between conspecific hosts at one collecting locality. The faunal composition of the 2 marsupial families which harboured ciliates differed greatly: the vombatid fauna was composed exclusively of amylovoracids whereas the macropodids harboured amylovoracids, polycostids and macropodiniids. In comparison to the ciliate fauna of ruminants, the fauna of macropodids is both depauperate and much more host specific. Low species richness in each host may be due to the large numbers of stomach nematodes in macropodids which compete with and may prey upon the ciliates within the stomach. The high levels of host specificity are probably due to different patterns of ciliate transmission in macropodids as they do not ruminate, eructate or feed indiscriminantly on pasture contaminated with saliva containing ciliates.

The value of idiosyncratic markers and changes to conserved tRNA sequences from the mitochondrial genome of hard ticks (Acari: Ixodida: Ixodidae) for phylogenetic inference

Idiosyncratic markers are features of genes and genomes that are so unusual that it is unlikely that they evolved more than once in a lineage of organisms. Here we explore further the potential of idiosyncratic markers and changes to typically conserved tRNA sequences for phylogenetic inference. Hard ticks were chosen as the model group because their phylogeny has been studied extensively. Fifty-eight candidate markers from hard ticks ( family Ixodidae) and 22 markers from the subfamily Rhipicephalinae sensu lato were mapped onto phylogenies of these groups. Two of the most interesting markers, features of the secondary structure of two different tRNAs, gave strong support to the hypothesis that species of the Prostriata ( Ixodes spp.) are monophyletic. Previous analyses of genes and morphology did not strongly support this relationship, instead suggesting that the Prostriata is paraphyletic with respect to the Metastriata ( the rest of the hard ticks). Parallel or convergent evolution was not found in the arrangements of mitochondrial genes in ticks nor were there any reversals to the ancestral arthropod character state. Many of the markers identified were phylogenetically informative, whereas others should be informative with study of additional taxa. Idiosyncratic markers and changes to typically conserved nucleotides in tRNAs that are phylogenetically informative were common in this data set, and thus these types of markers might be found in other organisms.

The highly rearranged mitochondrial genome of the plague thrips, Thrips imaginis (Insecta : thysanoptera): Convergence of two novel gene boundaries and an extraordinary arrangement of rRNA genes

To help understand the mechanisms of gene rearrangement in the mitochondrial (mt) genomes of hemipteroid insects, we sequenced the mt genome of the plague thrips, Thrips imaginis (Thysanoptera). This genome is circular, 15,407 by long, and has many unusual features, including (1) rRNA genes inverted and distant from one another, (2) an extra gene for tRNA-Ser, (3) a tRNA-Val lacking a D-arm, (4) two pseudo-tRNA genes, (5) duplicate control regions, and (6) translocations and/or inversions of 24 of the 37 genes. The mechanism of rRNA gene transcription in T. imaginis may be different from that of other arthropods since the two rRNA genes have inverted and are distant from one another. Further, the rRNA genes are not adjacent or even close to either of the two control regions. Tandem duplication and deletion is a plausible model for the evolution of duplicate control regions and for the gene translocations, but intramitochondrial recombination may account for the gene inversions in T. imaginis. All the 18 genes between control regions #1 and #2 have translocated and/or inverted, whereas only six of the 20 genes outside this region have translocated and/or inverted. Moreover, the extra tRNA gene and the two pseudo-tRNA genes are either in this region or immediately adjacent to one of the control regions. These observations suggest that tandem duplication and deletion may be facilitated by the duplicate control regions and may have occurred a number of times in the lineage leading to T. imaginis. T. imaginis shares two novel gene boundaries with a lepidopsocid species from another order of hemipteroid insects, the Psocoptera. The evidence available suggests that these shared gene boundaries evolved by convergence and thus are not informative for the interordinal phylogeny of hemipteroid insects. We discuss the potential of hemipteroid insects as a model system for studies of the evolution of animal rut genomes and outline some fundamental questions that may be addressed with this system.

Rates of gene rearrangement and nucleotide substitution are correlated in the mitochondrial genomes of insects

A number of studies indicated that lineages of animals with high rates of mitochondrial (mt) gene rearrangement might have high rates of mt nucleotide substitution. We chose the hemipteroid assemblage and the Insecta to test the idea that rates of mt gene rearrangement and mt nucleotide substitution are correlated. For this purpose, we sequenced the mt genome of a lepidopsocid from the Psocoptera, the only order of hemipteroid insects for which an entire mtDNA sequence is not available. The mt genome of this lepidopsocid is circular, 16,924 bp long, and contains 37 genes and a putative control region; seven tRNA genes and a protein-coding gene in this genome have changed positions relative to the ancestral arrangement of mt genes of insects. We then compared the relative rates of nucleotide substitution among species from each of the four orders of hemipteroid insects and among the 20 insects whose mt genomes have been sequenced entirely. All comparisons among the hernipteroid insects showed that species with higher rates of gene rearrangement also had significantly higher rates of nucleotide substitution statistically than did species with lower rates of gene rearrangement. In comparisons among the 20 insects, where the mt genomes of the two species differed by more than five breakpoints, the more rearranged species always had a significantly higher rate of nucleotide substitution than the less rearranged species. However, in comparisons where the mt genomes of two species differed by five or less breakpoints, the more rearranged species did not always have a significantly higher rate of nucleotide substitution than the less rearranged species. We tested the statistical significance of the correlation between the rates of mt gene rearrangement and mt nucleotide substitution with nine pairs of insects that were phylogenetically independent from one 2 another. We found that the correlation was positive and statistically significant (R-2 = 0.73, P = 0.01; R-s = 0.67, P < 0.05). We propose that increased rates of nucleotide substitution may lead to increased rates of gene rearrangement in the mt genomes of insects.