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PubMed2006

Wolbachia transinfection in Aedes aegypti: a potential gene driver of dengue vectors.

The endosymbiotic bacteria in the genus Wolbachia are capable of inducing a wide range of reproductive abnormalities in their hosts, including cytoplasmic incompatibility (CI), which could lead to the replacement of uninfected host populations with infected ones. Because of this, Wolbachia have attracted considerable interest as a potential mechanism for spreading disease-blocking transgenes through vector populations. Here we report the establishment of double Wolbachia transinfection by direct adult microinjection of Wolbachia from naturally double-infected Aedes albopictus to Aedes aegypti, the most important mosquito vector of infectious viral diseases, and a mosquito in which natural Wolbachia infections are not known to occur. We further demonstrate that incomplete CI is induced in these double-transinfected mosquitoes. Comparisons of fitness traits between naturally uninfected and transinfected Ae. aegypti lines indicated one significant difference in favor of the latter, namely, an increased number of eggs laid. Levels of CI expression corresponded to the Wolbachia density. There were large differences in relative Wolbachia density between reproductive and nonreproductive tissues in both Ae. albopictus and transinfected Ae. aegypti, except Malpighian tubule, which implied the preferred establishment of Wolbachia within reproductive tissue. Results from a simulation model confirm that population replacement by transinfected Ae. aegypti is possible over time. The establishment of Wolbachia double infections in Ae. aegypti by direct adult microinjection and the demonstration of CI expression in this new host suggest that Wolbachia could be experimentally transferred into vector species and could also be used as a gene-driving system to genetically manipulate vector populations.

Aedes↗
PubMed1995

Wolbachia superinfections and the expression of cytoplasmic incompatibility.

Strains of Drosophila simulans from Riverside, California (DSR) and Hawaii (DSH) harbour distinct strains of the cytoplasmic incompatibility microorganism Wolbachia, resulting in the expression of bidirectional incompatibility when crossed. D. simulans lines carrying both of these (superinfected) Wolbachia strains were generated by the transfer of infected DSH cytoplasm into DSR embryos by microinjection. The superinfected flies were unidirectionally incompatible with both DSR and DSH individuals. As a result of this pattern, the superinfected state was observed to replace single infections in laboratory populations. The ability of the superinfection to spread was modulated by the production of singly infected offspring from superinfected mothers: strain segregation was observed under crowded larval rearing conditions. An inverse correlation between the penetrance of the cytoplasmic incompatibility phenotype and the degree of larval crowding was also observed. The findings have implications for the evolution of bidirectionally incompatible strains, and lead to the prediction that superinfections should be relatively common in field populations. Evidence for a natural superinfection in the mosquito Aedes albopictus is discussed. The results also have applied significance for the generation of insect lines capable of driving desirable genes into populations already infected with Wolbachia, thus allowing repeated opportunities for population replacement.

Aedes↗
PubMed1991

The component community structure of larval trematodes in the pulmonate snail Helisoma anceps.

Factors that affected the component community structure of larval trematodes in the pulmonate snail Helisoma anceps in Charlie's Pond, North Carolina, were studied over a 15-mo period using a multiple mark-recapture protocol. Patent infections of 8 species were observed in 1,485 of 4,899 snails examined. Reproductive activity, population size, and survival rate of the snail population were estimated to evaluate the extent of resource availability for the parasites. Antagonistic interactions between trematode species that occurred at the infracommunity level had a neglible effect on the composition and structure of the component community. The patterns observed at this level were related to temporal heterogeneity in the abundance of infective stages (mostly miracidia), differential responses of trematode species to the diverse and constantly changing distribution of snail size and abundance, differential mortality of snails infected with certain trematode species, constant recruitment of 1 trematode species over time, and the existence of predictable disturbances such as the complete mortality of the host population and recruitment of a replacement population during a 6-8 wk period. The last factor operated as a reset mechanism for this snail-trematode system once each year. A model of patch dynamics, with snails as patch resources, best explains the organization and dynamics of this system.

Animals↗
PubMed1988

Methods for replacement of malaria vector populations.

The prospects are reviewed of replacement of malaria vector populations by harmless mosquito populations by means of: (i) ecologically competitive non-vector species; (ii) natural selection due to the harmfulness of being infected; (iii) selection for insecticide resistance genes; (iv) meiotic drive; (v) negative heterosis; and (vi) hybrid dysgenesis. Serious difficulties exist with all of these approaches. At present 'dilution', i.e. release of insects carrying the desired genes without any system for forcing population replacement is the only available method. It avoids the disadvantage that, in constructing elaborate genetic 'packages', factors for low fitness may be irreversibly incorporated into them. It is debatable whether release of males only or both sexes should be attempted.

Animals↗
PubMed2006

Need for and receipt of hip and knee replacement--a national population survey.

OBJECTIVES: Hip and knee joint replacements are effective, and yet little is known about how closely the need for joint replacement matches supply in different population groups. Our objective was to compare the prevalence of existing joint replacements with that of need in population groups in England. METHODS: A total of 7101 people aged 60 yrs or older, representative of the population of England, were interviewed. Participants were asked about both receipt and need for joint replacement, socio-economic status and co-morbidity. 'Need' classification was based on hip or knee pain and difficulty walking, with adjustment for potential surgical contraindications. Associations between participants' characteristics and both need and receipt were estimated. RESULTS: The prevalence of existing joint replacement (receipt) was 6% [95% confidence intervals (CI) 5, 6], and this was lower in the North than the South [adjusted odds ratio (OR) 0.72, CI 0.53, 0.96]. In contrast, the prevalence of estimated need was higher in the North (OR 1.27, CI 1.03, 1.58). Need was greater in women than men (OR 1.30, CI 1.09, 1.53), and showed an increasing gradient from the wealthiest to poorest quintile (ORs 1.00, 1.52, 2.18, 2.49, 3.23). In contrast, receipt did not differ significantly by sex or socio-economic group. CONCLUSIONS: People living in the North of England, women and the less wealthy experience relatively high levels of need, yet do not receive relatively more hip and knee joint replacements.

Aged↗
PubMed2006

Home haemodialysis-international trends and variation.

BACKGROUND: Home haemodialysis (HD) has the best patient outcomes and is the most cost-effective of any dialysis modality, but its use has been declining in many countries. METHODS: Point prevalence rates of different dialysis modalities and transplantation were obtained from national and regional registries for the most recent available year (2001-03) for 21 high-income and 12 middle-income countries. Relationships with median age and prevalence of diabetic nephropathy, healthcare expenditure and population density were assessed. Long-term trends in the use of home HD during the last two to four decades were obtained for seven countries. RESULTS: The prevalence of home HD varies from 0 to 58.4 per million population, and varies between countries, more than any other renal replacement therapy (RRT) modality. There is a positive association between the use of peritoneal dialysis and home HD (Spearman's rho = 0.531, P = 0.013), but no correlation with transplantation prevalence. There is a negative correlation with median age of the renal replacement population (rho = -0.552, P = 0.018). There is no association with prevalence of diabetic nephropathy, healthcare expenditure or population density. Temporal trends in home HD prevalence are dramatically different in different countries, with several countries expanding its use in the last few years. CONCLUSION: The use of home HD varies dramatically between and within countries. The variation cannot be explained by the variation in the use of other RRT modalities, nor by prevalence of diabetic nephropathy, national wealth or population density. The inverse correlation with median age is difficult to explain. Significant expansion of home HD is likely to be possible in most countries, and will be increasingly important as the impressive results of more frequent HD gain credence.

Health Services Needs and Demand↗
PubMed2004

Genetic evaluation of a proposed introduction: the case of the greater prairie chicken and the extinct heath hen.

Population introduction is an important tool for ecosystem restoration. However, before introductions should be conducted, it is important to evaluate the genetic, phenotypic and ecological suitability of possible replacement populations. Careful genetic analysis is particularly important if it is suspected that the extirpated population was unique or genetically divergent. On the island of Martha's Vineyard, Massachusetts, the introduction of greater prairie chickens (Tympanuchus cupido pinnatus) to replace the extinct heath hen (T. cupido cupido) is being considered as part of an ecosystem restoration project. Martha's Vineyard was home to the last remaining heath hen population until its extinction in 1932. We conducted this study to aid in determining the suitability of greater prairie chickens as a possible replacement for the heath hen. We examined mitochondrial control region sequences from extant populations of all prairie grouse species (Tympanuchus) and from museum skin heath hen specimens. Our data suggest that the Martha's Vineyard heath hen population represents a divergent mitochondrial lineage. This result is attributable either to a long period of geographical isolation from other prairie grouse populations or to a population bottleneck resulting from human disturbance. The mtDNA diagnosability of the heath hen contrasts with the network of mtDNA haplotypes of other prairie grouse (T. cupido attwateri, T. pallidicinctus and T. phasianellus), which do not form distinguishable mtDNA groupings. Our findings suggest that the Martha's Vineyard heath hen was more genetically isolated than are current populations of prairie grouse and place the emphasis for future research on examining prairie grouse adaptations to different habitat types to assess ecological exchangeability between heath hens and greater prairie chickens.

Animals↗
PubMed2006

oskar gene expression in the vector mosquitoes, Anopheles gambiae and Aedes aegypti.

A disease control strategy based on the introduction into mosquito populations of a gene conferring a pathogen-refractory phenotype is currently under investigation. This population replacement approach requires a drive system that will quickly spread and fix antipathogen effector genes in target populations. Modified transposable elements containing the control sequences of developmentally regulated genes may provide the basis for a gene drive system that regulates gene mobilization in a sex- and stage-restrictive manner. Screening of a Drosophila melanogaster database for genes whose products localize exclusively in the future germ cells during early embryonic development resulted in the identification of several candidate genes. The regulatory sequences of these genes could be used to drive transposition. Mosquito orthologous genes of oskar were identified based on sequence homology and characterized further. The tissue- and sex-specific expression profiles and hybridizations in situ show that oskar orthologous transcripts in Anopheles gambiae and Aedes aegypti accumulate in developing oocytes of adult females and localize to the posterior poles of early embryos. These characteristics potentiate the use of the regulatory sequences of mosquito oskar genes for the control of modified transposable elements.

Aedes↗
PubMed2003

Explanations of the fertility crisis in modern societies: a search for commonalities.

Near-global fertility decline began in the 1960s, and from the 1980s an increasing number of European countries and some Asian ones achieved very low fertility (total fertility below 1.5) with little likelihood of completed cohort fertility reaching replacement level. Earlier theory aiming at explaining this phenomenon stressed the incompatibility between post-industrial society and behaviour necessary for population replacement. Recent theory has been more specific, often concentrating on the current Italian or Spanish situations or on the contrast between them and the situation in either Scandinavia or the English-speaking countries, or both. Such an approach ignores important evidence, especially that from German-speaking populations. The models available concentrate on welfare systems and family expenses, omitting circumstances that may be unique to individual countries or longer-term factors that may be common to all.

Fertility↗
PubMed2005

Gene drive systems in mosquitoes: rules of the road.

Population replacement strategies for controlling transmission of mosquito-borne diseases call for the introgression of antipathogen effector genes into vector populations. It is anticipated that these genes, if present at high enough frequencies, will impede transmission of the target pathogens and result in reduced human morbidity and mortality. Recent laboratory successes in the development of virus- and protozoan-resistant mosquito strains make urgent research of gene drive systems capable of moving effector genes into wild populations. A systematic approach to developing safe and effective gene drive systems that includes defining the requirements of the system, identifying naturally occurring or synthetic genetic mechanisms for gene spread upon which drive systems can be based and the successful adaptation of a mechanism to a drive system, should mitigate concerns about using genetically engineered mosquitoes for disease control.

Animals↗
PubMed2002

Mutualistic Wolbachia infection in Aedes albopictus: accelerating cytoplasmic drive.

Maternally inherited rickettsial symbionts of the genus Wolbachia occur commonly in arthropods, often behaving as reproductive parasites by manipulating host reproduction to enhance the vertical transmission of infections. One manipulation is cytoplasmic incompatibility (CI), which causes a significant reduction in brood hatch and promotes the spread of the maternally inherited Wolbachia infection into the host population (i.e., cytoplasmic drive). Here, we have examined a Wolbachia superinfection in the mosquito Aedes albopictus and found the infection to be associated with both cytoplasmic incompatibility and increased host fecundity. Relative to uninfected females, infected females live longer, produce more eggs, and have higher hatching rates in compatible crosses. A model describing Wolbachia infection dynamics predicts that increased fecundity will accelerate cytoplasmic drive rates. To test this hypothesis, we used population cages to examine the rate at which Wolbachia invades an uninfected Ae. albopictus population. The observed cytoplasmic drive rates were consistent with model predictions for a CI-inducing Wolbachia infection that increases host fecundity. We discuss the relevance of these results to both the evolution of Wolbachia symbioses and proposed applied strategies for the use of Wolbachia infections to drive desired transgenes through natural populations (i.e., population replacement strategies).

Aedes↗
PubMedDate not supplied

Age structure of adult mosquito (Diptera: Culicidae) populations from Buenos Aires Province, Argentina.

In order to detect seasonal trends in the age structure of adult mosquitoes from Buenos Aires province, Argentina, female populations were sampled with CDC traps during 1989-1991 in Punta Lara and La Plata. The mosquitoes were dissected and age-grouped according to ovarian tracheation and ovariolar stages. All Runchomyia paranensis females were parous, suggesting that this species could be autogenous. Aedes albifasciatus showed parous peaks following population peaks, with shorter delays in spring-summer and longer in fall-winter. Ae. crinifer and Culex dolosus showed wide fluctuations in age structure due to adult emergences during all months. Psorophora ferox showed high population replacement rates. Mansonia indubitans and Ma. titillans have few generations per year during their activity period. This is the first report on age-grading of adults of field mosquito populations from Argentina.

Age Distribution↗
PubMedDate not supplied

Managed care and critical pathway development: the joint replacement experience.

This article examines the economic, social, ethical, and political issues affecting total joint replacement patients in a managed care environment. Using general systems theory as a framework, it examines the interrelated historical events that have shaped the development of both joint replacement procedures and managed care, and discusses the extent to which these two phenomena have been mutually influential. Specifically, the article examines the initial development, implementation, and continuing evolution of clinical pathways as an easily identified and relatively discrete manifestation of managed care for the joint replacement population. While the overall impact of managed care is beyond the scope of this presentation, it is hoped that a focus on the practical application of clinical pathways to joint replacement will allow some general principles to emerge that may be useful for both patients and practitioners operating in other aspects of the managed care environment.

Arthroplasty, Replacement↗
PubMed1999

Ablation of a specific cell population by the replacement of a uniquely expressed gene with a toxin gene.

The transgenic expression of a toxin gene or a thymidine kinase gene under the control of cell type-specific promoter/enhancer has been shown to be useful for removing a specific cell population in mice. However, this approach requires extensive analysis of the control elements for gene expression in the preparation of the transgenic constructs, and furthermore, the toxin gene might be expressed ectopically because of random integration, resulting in aberrant depletion of unrelated cells. To avoid such difficulties with the transgenic approach, we established a method for the specific depletion of a cell population by replacing a uniquely expressed gene in the population with the diphtheria toxin gene by using homologous recombination. The NKR-P1 gene, a specific cell surface marker of natural killer (NK) cells, was selected as the target gene for depleting NK cells. In chimeric mice reconstituted with embryonic stem cells in which the NKR-P1 gene was replaced by the toxin gene, NKR-P1(+) cells were almost completely depleted, and NK cell function was abrogated in the embryonic stem cell-derived lymphoid cells. Other cell lineages developed normally. These results show that all NK cells express NKR-P1, that NKR-P1(+) cells do not influence the development of T and B cells, and further, that this technology of cell targeting is a fast and powerful method of generating mice lacking any chosen cell population.

Animals↗
PubMed2002

Wolbachia as a potential tool for suppressing filarial transmission.

There is currently a great deal of interest in Wolbachia because of their wide distribution in arthropods and filarial nematodes and their striking effects on the biology of their hosts, including a possible role in speciation. They manipulate the reproduction of arthropod hosts through various effects on their hosts' biology, particularly cytoplasmic incompatibility (CI), to increase the proportion of infected individuals in the population, often to the point of fixation. This ability of Wolbachia to sweep through host populations indicates several potential applications of Wolbachia in the control of mosquito-borne disease. One uses Wolbachia-induced CI as a form of sterile-insect technique, to suppress mosquito populations. Another envisages the application of CI for population replacement, with the intention of preventing the transmission of human pathogens, by substituting desirable genotypes, including those carried in transgenes. A third possibility is to use Wolbachia to reduce the survival of mosquito populations and thereby reduce their ability to transmit the infection. This article provides an overview of the biological effects of Wolbachia on arthropod hosts, with discussion of the possible future exploitation of these effects in the control of filariasis.

Animals↗
PubMed1980

Technical dilemmas in portacaval shunt operations as a consequence of replaced right hepatic artery.

Surgical procedures designed to decompress the portal venous system in patients with cirrhosis and bleeing esophageal varices may be complicated by anatomic variations in the extrahepatic arterial circulation. Anomalous right hepatic arteries which arise from the superior mesenteric artery may be encountered in 18 to 20 per cent of the normal population. Replaced arteries are not accessory vessels but rather provide the sole arteries circulation to well defined segments of the liver. Unfortunate injury may result in severe ischemic truama of the liver. Preoperative vicseral arteriography is essential prior to any contemplated portosystemic shunt procedure. The unusual anatomic relationship of such an anomalous right to hepatic artery to the portal vein may contraindicate standard portacaval, interposition portacaval or portarnal shunt procedures; graft angulation and anastomotic distortion may jeopardize shunt patancy and result in recurrent variceal hemmorrhage. A technique for portal vein-hepatic artery transposition and end-to-side portacaval shunt is presented as a feasible alternative if anomalies of the hepatic artery preclude standard shunt procedures.

Hepatic Artery↗
PubMed2005

Evolution of searching and life history characteristics in individual-based models of host-parasitoid-microbe associations.

In this paper we develop a novel discrete, individual-based mathematical model of the evolution of life history, dispersal and other behavioural characteristics in insect host-parasitoid-microbe associations, and use it to investigate their evolutionary dynamics. For any individual characteristic the model begins with an even, rectangular distribution of characteristic values. Selection is then allowed to act, and the change in the distribution of the characteristic values is observed. Evolutionary change in the population variance of the characteristic value is also observed, since we would expect this to decline under selection in most cases. The paper, therefore, introduces a general framework for modeling problems of evolution in stochastic, spatially structured environments, where movement and dispersal are under selection. The model then extends this approach to include the sex-distorting bacterium Wolbachia in order to investigate aspects of its horizontal and vertical transmission under different levels of superparasitism by parasitoids. The model also includes a neutral genetic marker, in order to be able to detect changes in phenotype frequency caused by genetic drift, as well as a simplified simulation of sexual reproduction so as to allow the possibility of recombination between genotypes. Key results from the model simulations show that: (i) the refractory time after oviposition affects the value of superparasitism, with short refractory times favouring high rates of superparasitism; (ii) variable levels of superparasitism do not affect the stable proportion of the population of parasitoids infected with Wolbachia, but this is achieved by different evolutionary pathways under low and high superparasitism, respectively. In the case of low superparasitism Wolbachia spreads mainly by vertical transmission, leading to population replacement, whereas when superparasitism rates are high there is significant horizontal transfer.

Animals↗
PubMed1994

Replacement of diseased mouse liver by hepatic cell transplantation.

Adult liver has the unusual ability to fully regenerate after injury. Although regeneration is accomplished by the division of mature hepatocytes, the replicative potential of these cells is unknown. Here, the replicative capacity of adult liver cells and their medical usefulness as donor cells for transplantation were investigated by transfer of adult mouse liver cells into transgenic mice that display an endogenous defect in hepatic growth potential and function. The transplanted liver cell populations replaced up to 80 percent of the diseased recipient liver. These findings demonstrate the enormous growth potential of adult hepatocytes, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma.

Animals↗