The system of genetic exchange in <i>Trypanosoma brucei</i> and other trypanosomatids

In this chapter, we discuss our current understanding of the systems of genetic exchange in trypanosomatids and the im-pact the recent genome projects have had on this area of research. We focus mainly on the details of Trypanosoma brucei as it is the most extensively studied of the “trityps”, but will also refer to a recently discovered novel mechanism of genetic exchange in T. cruzi and the apparent rarity of genetic ex-change in Leishmania sp.The system of genetic exchange in Trypanosoma brucei has been known to exist since the late eighties when a genetic cross between different strains was carried out by co-transmission through the tsetse fly. We discuss the segregation of nuclear, chromosomal and kDNA markers and outline the two current models for the mechanism of genetic exchange. We also present how the completion of the genome project has allowed the identification of polymorphic micro and minisatel-lite markers distributed throughout the genome, which have been used to prove formally that meiosis, independent assortment and crossing over occur in this para-site, as would be predicted in a conventional Mendelian system. Such data have been used to construct the first genetic map of T. brucei, which opens up the use of genetic analysis, coupled with positional cloning and the genome sequence, as a tool to identify the genes involved in a range of traits relevant to the disease

Pictorial Socratic dialogue and conceptual change

Counter-examples used in a Socratic dialogue aim to provoke reflection to effect conceptual changes. However, natural language forms of Socratic dialogues have their limitations. To address this problem, we propose an alternative form of Socratic dialogue called the pictorial Socratic dialogue. A Spring Balance System has been designed to provide a platform for the investigation of the effects of this pedagogy on conceptual changes. This system allows learners to run and observe an experiment. Qualitative Cartesian graphs are employed for learners to represent their solutions. Indirect and intelligent feedback is prescribed through two approaches in the pictorial Socratic dialogue which aim to provoke learners probe through the perceptual structural features of the problem and solution, into the deeper level of the simulation where Archimedes’ Principle governs

Molecular epidemiology of African sleeping sickness

Human sleeping sickness in Africa, caused by Trypanosoma brucei spp. raises a number of questions. Despite the widespread distribution of the tsetse vectors and animal trypanosomiasis, human disease is only found in discrete foci which periodically give rise to epidemics followed by periods of endemicity A key to unravelling this puzzle is a detailed knowledge of the aetiological agents responsible for different patterns of disease--knowledge that is difficult to achieve using traditional microscopy. The science of molecular epidemiology has developed a range of tools which have enabled us to accurately identify taxonomic groups at all levels (species, subspecies, populations, strains and isolates). Using these tools, we can now investigate the genetic interactions within and between populations of Trypanosoma brucei and gain an understanding of the distinction between human- and nonhuman-infective subspecies. In this review, we discuss the development of these tools, their advantages and disadvantages and describe how they have been used to understand parasite genetic diversity, the origin of epidemics, the role of reservoir hosts and the population structure. Using the specific case of T.b. rhodesiense in Uganda, we illustrate how molecular epidemiology has enabled us to construct a more detailed understanding of the origins, generation and dynamics of sleeping sickness epidemics

Distributed resource discovery using a context sensitive infrastructure

Distributed Resource Discovery in a World Wide Web environment using full-text indices will never scale. The distinct properties of WWW information (volume, rate of change, topical diversity) limits the scaleability of traditional approaches to distributed Resource Discovery. An approach combining metadata clustering and query routing can, on the other hand, be proven to scale much better. This paper presents the Content-Sensitive Infrastructure, which is a design building on these results. We also present an analytical framework for comparing scaleability of different distribution strategies

Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata

&lt;b&gt;BACKGROUND&lt;/b&gt;: Little is known about how apicomplexan parasites have evolved to infect different host species and cell types. Theileria annulata and Theileria parva invade and transform bovine leukocytes but each species favours a different host cell lineage. Parasite-encoded proteins secreted from the intracellular macroschizont stage within the leukocyte represent a critical interface between host and pathogen systems. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species. We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. These families represent a well-characterised group of genes implicated in control of the host cell phenotype and a gene family of unknown function. To gain further insight into their evolution and function, this study investigates whether representative genes of these two families are diversifying or constrained within the T. annulata population. &lt;b&gt;RESULTS&lt;/b&gt;: Strong evidence is provided that the sub-telomerically encoded SVSP family and the host-nucleus targeted TashAT family have evolved under contrasting pressures within natural T. annulata populations. SVSP genes were found to possess atypical codon usage and be evolving neutrally, with high levels of nucleotide substitutions and multiple indels. No evidence of geographical sub-structuring of allelic sequences was found. In contrast, TashAT family genes, implicated in control of host cell gene expression, are strongly conserved at the protein level and geographically sub-structured allelic sequences were identified among Tunisian and Turkish isolates. Although different copy numbers of DNA binding motifs were identified in alleles of TashAT proteins, motif periodicity was strongly maintained, implying conserved functional activity of these sites. &lt;b&gt;CONCLUSIONS&lt;/b&gt;: This analysis provides evidence that two distinct secretome genes families have evolved under contrasting selective pressures. The data supports current hypotheses regarding the biological role of TashAT family proteins in the management of host cell phenotype that may have evolved to allow adaptation of T. annulata to a specific host cell lineage. We provide new evidence of extensive allelic diversity in representative members of the enigmatic SVSP gene family, which supports a putative role for the encoded products in subversion of the host immune response

Human infectivity trait in <i>Trypanosoma brucei</i>: stability, heritability and relationship to sra expression

Some Trypanosoma brucei lines infect humans whereas others do not because the parasites are lysed by human serum. We have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. This method has been used to discriminate between 3 classes of human serum resistance; sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T. brucei genome project, is intermediate. The phenotype is expressed in both bloodstream and metacyclic forms, is stably expressed during chromic infections and on cyclical transmission through tsetse flies. Trypanosomes of intermediate phenotype are distinguished from sensitive populations of cells by the slower rate of lysis and by the potential to become fully resistant to killing by human serum as a result of selection or long-term serial passaging in mice, and to pass on full resistance phenotype to its progeny in a genetic cross. The sra gene has been shown previously to determine human serum resistance in T. brucei but screening for the presence and expression of this gene indicated that it is not responsible for the human serum resistance phenotype in the trypanosome lines that we have examined, indicating that an alternative mechanism for HSR exists in these stocks. Examination of the inheritance of the phenotype in F1 hybrids for both bloodstream and metacyclic stages from 2 genetic crosses demonstrated that the phenotype is co-inherited in both life-cycle stages in a manner consistent with being a Mendelian trait, determined by only one or a few genes

Living in the slow or fast lane: cognitive phenotypes in honeybees

2021 Spring.Includes bibliographical references.The evolution and maintenance of cognitive variation is a question of fundamental interest in animal behavior because differences in cognition are predicted to underlie differences in behavior. The correlation between behavioral and cognitive variation has largely been conceptualized in terms of the speed-accuracy trade-off driving alternative cognitive strategies where 'fast' individuals are superficial learners that make inaccurate, risk-prone decisions relative to 'slow' individuals. My research has explored the factors that select for different cognitive abilities across species and the mechanisms that maintain variation in cognitive ability within species. To address these questions, I have identified how individuals of four honeybee species (Apis mellifera, A. cerana, A. dorsata, A. florea) differ in performance on multiple cognitive tasks and explored how such variation translates to behavioral outcomes and is shaped by ecology. In chapter one, I tested for the presence of variation in two different learning abilities in honeybee foragers and whether any component of learning influenced wing damage, an indicator of survival. My results demonstrated considerable interindividual variation in different types of learning abilities such that landmark and olfactory learning were negatively correlated. Additionally, I found that olfactory learning was positively correlated with maneuverability performance during flight, a measure which in turn positively influenced wing damage, a proxy for survival. This experiment demonstrated that individuals differ considerably in how they perform on two cognitive tasks and that cognitive ability has important implications for behaviors associated with survival. This work was further explored in chapter 2, where I studied how differences in learning preference relate to decision making during foraging. I measured individual latency to learn on a solitary foraging task and latency to learn on a social foraging task and found that individuals that perform well in a solitary learning task perform poorly in a social learning task. These findings suggest that honeybees specialize in one type of learning strategy when making foraging decisions, and such differences may have important implications for how individuals provision their colony. The first two chapters focused on how differences in performance on cognitive tasks may represent a trade-off that correlates to different behaviors. In the latter half of my dissertation, I first used multiple cognitive traits to define a cognitive phenotype in an individual and then investigated how such differences might impact performance on multiple behaviors and life history traits to determine functional consequences of cognitive variation. I then expanded this research to determine how differences in ecology shape cognitive phenotypes. In chapter three, I tested for the presence of distinct cognitive phenotypes in A. mellifera foragers by measuring multiple cognitive traits and determining whether these traits covary to produce distinct slow and fast cognitive phenotypes. I then compared performance on multiple behavioral and life history tasks to see if there were functional differences between these cognitive types. My results indicate the presence of two cognitive phenotypes that meet the predictions of the speed-accuracy trade-off and that are conserved across colonies. Compared to slow bees, fast bees were described by high associative learning, high preference for novelty and high preference for variance, bees which also engage in more nursing behavior and transition to becoming a forager at an earlier age. In chapter four, which explored how ecological and life history differences shape cognitive phenotypes between closely related honeybee species, I tested for differences in the cognitive phenotype in four honeybee species, each of which occupied a unique ecological niche that was correlated to their position on the slow-fast life history axis. My results indicate that a set of cognitive traits consistently covary within each species, resulting in slow and fast cognitive phenotypes that meet the predictions of the speed-accuracy tradeoff. I also found that the four species do not align on a slow-fast cognitive axis due to known differences in their life history and nesting ecology. Rather, cognitive differences among the species appear correlated to their brain size, which may be driven by differences in foraging range. Taken together, this work indicates that cognitive variation at the individual level has important behavioral and life history outcomes that may impact how the individual interacts with their environment and how the colony performs. At the species level, cognitive variation appears to be driven by a complex relationship with the species unique environment as well as underlying trade-offs associated with costs of cognition