Browsing by Issue Date, starting with "2004"
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- Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectivesPublication . Gomes, M. G. M.; White, L. J.; Medley, G. F.The SIR (susceptible-infectious-resistant) and SIS (susceptible-infectious-susceptible) frameworks for infectious disease have been extensively studied and successfully applied. They implicitly assume the upper and lower limits of the range of possibilities for host immune response. However, the majority of infections do not fall into either of these extreme categories. We combine two general avenues that straddle this range: temporary immune protection (immunity wanes over time since infection), and partial immune protection (immunity is not fully protective but reduces the risk of reinfection). We present a systematic analysis of the dynamics and equilibrium properties of these models in comparison to SIR and SIS, and analyse the outcome of vaccination programmes. We describe how the waning of immunity shortens inter-epidemic periods, and poses major difficulties to disease eradication. We identify a "reinfection threshold" in transmission when partial immunity is included. Below the reinfection threshold primary infection dominates, levels of infection are low, and vaccination is highly effective (approximately an SIR model). Above the reinfection threshold reinfection dominates, levels of infection are high, and vaccination fails to protect (approximately an SIS situation). This association between high prevalence of infection and vaccine failure emphasizes the problems of controlling recurrent infections in high-burden regions. However, vaccines that induce a better protection than natural infection have the potential to increase the reinfection threshold, and therefore constitute interventions with a surprisingly high capacity to reduce infection where reduction is most needed
- Modelos de interacção genética de dois genes em fenótiposPublication . Sepúlveda, Nuno; Paulino, C.D.; Penha-Gonçalves, CarlosEm trabalhos anteriores foram propostos diversos modelos estatísticos para a penetrância de forma a inferir a interacção de dois genes dial´elicos na construção de fenótipos binários complexos: modelos de acção independente, modelos de inibição e modelos de número mínimo de alelos. Estes modelos baseiam-se numa decomposição da penetrância através da abordagem por penetrâncias alélicas, que permitiu a inclusão dos conceitos mendelianos de dominância e recessividade alélica na sua modelação. Pretende-se aqui dar a conhecer os avanços mais recentes na parte da modelação da interacção genética, apresentando uma nova decomposição da penetrância e uma nova formulação matemática da dominância e da recessividade. Aplicam-se ainda ferramentas bayesianas para o ajustamento dos modelos de interacção genética a dados experimentais com recurso ao método de amostragem de Gibbs. Toda a metodologia é exemplificada num conjunto de dados de um estudo da susceptibilidade da malária cerebral em ratinhos.
- The reinfection threshold promotes variability in tuberculosis epidemiology and vaccine efficacyPublication . Gomes, M. G. M.; Franco, A. O.; Gomes, M. C.; Medley, G. F.; Proceedings. Biological sciences, R.S.Population patterns of infection are determined largely by susceptibility to infection. Infection and vaccination induce an immune response that, typically, reduces susceptibility to subsequent infections. With a general epidemic model, we detect a 'reinfection threshold', above which reinfection is the principal type of transmission and, consequently, infection levels are much higher and vaccination fails. The model is further developed to address human tuberculosis (TB) and the impact of vaccination. The bacille Calmette-Guérin (BCG) is the only vaccine in current use against TB, and there is no consensus about its usefulness. Estimates of protection range from 0 to 80%, and this variability is aggravated by an association between low vaccine efficacy and high prevalence of the disease. We propose an explanation based on three postulates: (i) the potential for transmission varies between populations, owing to differences in socio-economic and environmental factors; (ii) exposure to mycobacteria induces an immune response that is partially protective against reinfection; and (iii) this protection is not significantly improved by BCG vaccination. These postulates combine to reproduce the observed trends, and this is attributed to a reinfection threshold intrinsic to the transmission dynamics. Finally, we demonstrate how reinfection thresholds can be manipulated by vaccination programmes, suggesting that they have a potentially powerful role in global control
- Nitric oxide is involved in growth regulation and re-orientation of pollen tubesPublication . Prado, AM; Porterfield, DM; Feijo, JANitric oxide (NO) controls diverse functions in many cells and organs of animals. It is also produced in plants and has a variety of effects, but little is known about their underlying mechanisms. In the present study, we have discovered a role for NO in the regulation of pollen tube growth, a fast tip-growing cellular system. Pollen tubes must be precisely oriented inside the anatomically complex female ovary in order to deliver sperm. We hypothesized that NO could play a role in this guidance and tested this hypothesis by challenging the growth of pollen tubes with an external NO point source. When a critical concentration was sensed, the growth rate was reduced and the growth axis underwent a subsequent sharp reorientation, after which normal growth was attained. This response was abrogated in the presence of the NO scavenger CPTIO and affected by drugs interfering in the cGMP signaling pathway. The sensitivity threshold of the response was significantly augmented by sildenafil citrate (SC), an inhibitor of cGMP-specific phosphodiesterases in animals. NO distribution inside pollen tubes was investigated using DAF2-DA and was shown to occur mostly in peroxisomes. Peroxisomes are normally excluded from the tip of pollen tubes and little if any NO is found in the cytosol of that region. Our data indicate that the rate and orientation of pollen tube growth is regulated by NO levels at the pollen tube tip and suggest that this NO function is mediated by cGMP.
- Adaptation of asexual populations under Muller’s ratchetPublication . Bachtrog, D.; Gordo, I.We study the population genetics of adaptation in nonequilibrium haploid asexual populations. We find that the accumulation of deleterious mutations, due to the operation of Muller’s ratchet, can considerably reduce the rate of fixation of advantageous alleles. Such reduction can be approximated reasonably well by a reduction in the effective population size. In the absence of Muller’s ratchet, a beneficial mutation can only become fixed if it creates the best possible genotype; if Muller’s ratchet operates, however, mutations initially arising in a nonoptimal genotype can also become fixed in the population, since the loss of the least-loaded class implies that an initially nonoptimal background can become optimal. We show that, while the rate at which adaptive mutations become fixed is reduced, the rate of fixation of deleterious mutations due to the ratchet is not changed by the presence of beneficial mutations as long as the rate of their occurrence is low and the deleterious effects of mutations (sd) are higher than the beneficial effects (sa). When sa . sd, the advantage of a beneficial mutation can outweigh the deleterious effects of associated mutations. Under these conditions, a beneficial allele can drag to fixation deleterious mutations initially associated with it at a higher rate than in the absence of advantageous alleles. We propose analytical approximations for the rates of accumulation of deleterious and beneficial mutations. Furthermore, when allowing for the possible occurrence of interference between beneficial alleles, we find that the presence of deleterious mutations of either very weak or very strong effect can marginally increase the rate of accumulation of beneficial mutations over that observed in the absence of such deleterious mutations.
- Putting fear in its place: remapping of hippocampal place cells during fear conditioningPublication . Moita, MAP; Rosis, S; Zhou, Y; LeDoux, JE; Blair, HTWe recorded hippocampal place cells in two spatial environments: a training environment in which rats underwent fear conditioning and a neutral control environment. Fear conditioning caused many place cells to alter ( or remap) their preferred firing locations in the training environment, whereas most cells remained stable in the control environment. This finding indicates that aversive reinforcement can induce place cell remapping even when the environment itself remains unchanged. Furthermore, contextual fear conditioning caused significantly more remapping of place cells than auditory fear conditioning, suggesting that place cell remapping was related to the rat's learned fear of the environment. These results suggest that one possible function of place cell remapping may be to generate new spatial representations of a single environment, which could help the animal to discriminate among different motivational contexts within that environment.
- Signalling by tipsPublication . Feijó, J.A.; Costa, S.S.; Prado, A.M.; Becker, J.D.; Certal, A.C.New molecules, including protein kinases, lipids and molecules that have neurotransmitter activities in animals have emerged as important players in tip-growing cells. Transcriptomics analysis reveals that the largest single class of genes expressed in pollen tubes encode signal transducers, reflecting the necessity to decode complex and diverse pathways that are associated with tip growth. Many of these pathways may use common intracellular second messengers, with ions and reactive oxygen species emerging as two major common denominators in many of the processes involved in tip growth. These second messengers might influence the actin cytoskeleton through known interactions with actin-binding proteins. In turn, changes in the dynamic properties of the cytoskeleton would define the basic polarity events needed to shape and modify tip-growing cells.
- Quantitative genetics of functional characters in Drosophila melanogaster populations subjected to laboratory selectionPublication . Teotónio, H; Matos, M; Rose, MRWhat are the genetics of phenotypes other than fitness, in outbred populations? To answer this question. the quantitative-genetic basis of divergence was characterized for outbred Drosophila melanogaster populations that had previously undergone selection to enhance characters related to fitness. Line-cross analysis using first-generation and second-generation hybrids from reciprocal crosses was conducted for two types of cross, each replicated fivefold. One type of cross was between representatives of the ancestral population, a set of five populations maintained for several hundred generations on a two-week discrete-generation life cycle and a set of five populations adapted to starvation stress. The other type of cross was between the same set of ancestral-representative populations and another set of five populations selected for accelerated development from egg to egg. Developmental time from coo to eclosion. starvation resistance, dry body weight and fecundity at day 14 from ego were fit to regression models estimating single-locus additive and dominant effects, maternal and paternal effects. and digenic additive and dominance epistatic effects. Additive genetic variation explained most of the differences between populations, with additive maternal and cytoplasmic effects also commonly found. Both within-locus and between-locus dominance effects were inferred in some cases, as well as one instance of additive epistasis. Some of these effects may have been caused by linkage disequilibrium. We conclude with a brief discussion concerning the relationship of the genetics of population differentiation to adaptation.