Integration of parasite genetic information in malaria transmission modelling

Mathematical models of malaria transmission are increasingly used to quantify the impact of malaria control efforts and to assist in the development and costing of future initiatives such as the WHO Global Technical Strategy for Malaria 2016-2030. These models have highlighted both the progress made so far, but also how continued investment is needed to reach the milestones required. However, the increase in global malaria cases reported in 2018 suggests that new tools may be required to continue the gains made and to address the growing risk of antimalarial resistance threatening to reverse the recent declines in malaria burden. The proliferation of genetic sequencing and the publication of the Plasmodium falciparum reference genome in 2002 has facilitated a greater understanding of the genetic determinants of resistance and molecular tools are subsequently poised to become a routine tool for malaria control. Consequently, integrating parasite genetic information into established models of malaria transmission models can contribute to both our understanding of the drivers and optimum policies for addressing resistance and detailing the potential of molecular tools within malaria control. Plasmodium falciparum is known to have evolved several times in response to first line antimalarials. However, recent evidence has shown evolution to rapid diagnostic tests. The WHO has consequently issued guidance advising national malaria control programmes to conduct surveillance for pfhrp2/3 deletions. The timing of this policy recommendation and my previous work modelling pfhrp2 deletions necessitated a timely extension of our previous model to evaluate the implications of seasonality in malaria transmission on estimates of the prevalence of pfhrp2/3 deletions. Recent studies have suggested that malaria genotyping could be a useful tool for epidemiological surveillance. By developing an extended version of an established model of malaria transmission, which now models individual mosquitoes affording the full parasite life cycle to be represented, I characterise the potential utility of malaria genomics for inferring changes in transmission intensity. I conclude that although molecular tools could enable accurate estimation of malaria prevalence, greater attention needs to be placed on the chosen sampling scheme, recording patient metadata and developing the statistical toolkit for analysing polyclonal infected individuals. In 2015, health ministers in the Greater Mekong Subregion (GMS) adopted the WHO strategy for malaria elimination in the GMS 2016-2030. The strategy was developed to accelerate elimination in South-East Asia, which is currently the best approach to address the growing threat of artemisinin resistance and the emergence of multidrug resistant parasite lineages. In response, I demonstrate how the therapeutic lifespan of the five currently recommended artemisinin combination therapies can be prolonged by reducing antimalarial overprescription by ensuring that all suspected malaria fevers are tested before administering antimalarials. I conclude by comparing different cycling and mixing strategies before reviewing how each strategy can be improved to slow the spread of antimalarial resistance. Elimination in the GMS is undoubtedly an effective mechanism for preventing the spread of artemisinin resistance to Africa. However, if efforts to eliminate by 2030 have failed it will be imperative to understand the mechanisms with which resistance may continue to spread. To this extent, the capability of resistant strains to invade susceptible populations is evaluated using data from standard membrane feeding assays. Findings are incorporated in the transmission model to quantify the transmission advantage of artemisinin resistance at the population level.Open Acces

A comprehensive, multi-process box-model approach to glacial-interglacial carbon cycling

The canonical question of which physical, chemical or biological mechanisms were responsible for oceanic uptake of atmospheric CO2 during the last glacial is yet unanswered. Insight from paleo proxies has led to a multitude of hypotheses but none so far have been convincingly supported in three dimensional numerical modelling experiments. The processes that influence the CO2 uptake and export production are inter-related and too complex to solve conceptually while complex numerical models are time consuming and expensive to run which severely limits the combinations of mechanisms that can be explored. Instead, an intermediate inverse box model approach is used here in which the whole parameter space is explored. The glacial circulation and biological production states are derived from these using proxies of glacial export production and the need to draw down CO2 into the ocean. We find that circulation patterns which explain glacial observations include reduced Antarctic Bottom Water formation and high latitude mixing and to a lesser extent reduced equatorial upwelling. The proposed mechanism of CO2 uptake by an increase of eddies in the Southern Ocean, leading to a reduced residual circulation, is not supported. Regarding biological mechanisms, an increase in the nutrient utilization in either the equatorial regions or the northern polar latitudes can reduce atmospheric CO2 and satisfy proxies of glacial export production. Consistent with previous studies, CO2 is drawn down more easily through increased productivity in the Antarctic region than the sub-Antarctic, but that violates observations of lower export production there

What If Grassroots Don’t Take Root?: Reflections on Cultivating Communities of Practice

Traditionally, communities of practice (CoPs) have been characterized as selfdirected, self-governing entities. In our experience, however, we have found that CoPs focused on teaching and learning in post-secondary institutions rarely lead themselves. In this piece, we reflect on our experiences leading CoPs as organizers and facilitators. We then draw on literature about CoP governance to consider the implications of having educational developers – and post-secondary institutions more broadly – take on influential roles in managing CoPs. To conclude, we pose questions to guide future research on how to cultivate healthy CoPs and healthy roles for the educational developers who support them

Chromosomes of the Laboratory Mouse

The chromosome number of 40 for the laboratory mouse was confirmed. A karyotype of mouse chromosomes was made. The chromosomes can be arranged into four groups based on size and shape

The Optimist, The Pessimist, The Altruist

https://digitalcommons.library.umaine.edu/mmb-me/1699/thumbnail.jp

β-Cyclocitral, a Grazer Defence Signal Unique to the Cyanobacterium Microcystis

β-Cyclocitral is often present in eutrophic waters and is a well known source of airborne and drinking water malodor, but its production and functional ecology are unresolved. This volatile organic compound (VOC) is derived from the catalytic breakdown of β-carotene, and evidence indicates that it is produced by the activation of a specific carotene oxygenase by all species of the bloom-forming cyanobacterium Microcystis. Previous work has shown that β-cyclocitral affects grazer behavior, but the nature of this interaction and its influence on predator-prey dynamics was unresolved. The present study combined analytical and behavioral studies to evaluate this interaction by using Microcystis NRC-1 and Daphnia magna. Results showed that β-cyclocitral was undetectable in live Microcystis cells, or present only at extremely low concentrations (2.6 amol /cell). In contrast, cell rupture activated a rapid carotene oxygenase reaction, which produced high amounts (77 ± 5.5 amol β-cyclocitral/cell), corresponding to a calculated maximum intracellular concentration of 2.2mM. The behavioral response of Daphnia magna to β-cyclocitral was evaluated in a bbe© Daphnia toximeter, where β-cyclocitral treatments induced a marked increase in swimming velocity. Acclimation took place within a few minutes, when Daphnia returned to normal swimming velocity while still exposed to β-cyclocitral. The minimum VOC concentration (odor threshold) that elicited a significant grazer response was 750nM β-cyclocitral, some 2,900 times lower than the per capita yield of a growing Microcystis cell after activation. Under natural conditions, initial grazer-related or other mode of cell rupture would lead to the development of a robust β-cyclocitral microzone around Microcystis colonies, thus acting as both a powerful repellent and signal of poor quality food to grazer

Carrier localization mechanisms in InGaN/GaN quantum wells

Localization lengths of the electrons and holes in InGaN/GaN quantum wells have been calculated using numerical solutions of the effective mass Schr\"odinger equation. We have treated the distribution of indium atoms as random and found that the resultant fluctuations in alloy concentration can localize the carriers. By using a locally varying indium concentration function we have calculated the contribution to the potential energy of the carriers from band gap fluctuations, the deformation potential and the spontaneous and piezoelectric fields. We have considered the effect of well width fluctuations and found that these contribute to electron localization, but not to hole localization. We also simulate low temperature photoluminescence spectra and find good agreement with experiment.Comment: 7 pages, 7 figure