Adaptive immunity selects against malaria infection blocking mutations

The mutation responsible for Duffy negativity, which impedes Plasmodium vivax infection, has reached high frequencies in certain human populations. Conversely, mutations capable of blocking the more lethal P. falciparum have not succeeded in malarious zones. Here we present an evolutionary-epidemiological model of malaria which demonstrates that if adaptive immunity against the most virulent effects of malaria is gained rapidly by the host, mutations which prevent infection per se are unlikely to succeed. Our results (i) explain the rarity of strain-transcending P. falciparum infection blocking adaptations in humans; (ii) make the surprising prediction that mutations which block P. falciparum infection are most likely to be found in populations experiencing low or infrequent malaria transmission, and (iii) predict that immunity against some of the virulent effects of P. vivax malaria may be built up over the course of many infections

Germination responses of a dry sclerophyll forest soil-stored seedbank to fire related cues

Fire is an integral component of many ecosystems worldwide. Many plant species require fire-related cues, primarily heat and smoke, to trigger germination. Despite the importance of this process, the responses of many Australian species to these cues are unknown. Without this knowledge fire management strategies may be developed that are inappropriate for individual species and vegetation communities. In this study we examined the responses of a dry sclerophyll forest seed bank to heat and smoke germination cues. Analysis was possible for 48 taxa within the soil seedbank with 34 of these showing a response to one or both of the germination cues. 10 species responded to the heat treatment, 11 species responded to the smoke treatment and 13 species responded to both the heat and smoke treatments. Germination cues acted independently for all species considered. Results in this study were consistent with published reports for most species, although some differences were seen at the species and genus level. The study highlights the importance of fire-related cues in enhancing germination of a large proportion of the species occurring in dry sclerophyll forests

The Use of Recombinant Human Bone Morphogenetic Protein 2 (rhBMP-2) to Promote Spinal Fusion in a Nonhuman Primate Anterior Interbody Fusion Model

Study Design. A study on the efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in a nonhuman primate anterior interbody fusion model. Objectives. To investigate the efficacy of rhBMP-2 with an absorbable collagen sponge carrier to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Summary of Background Data. RhBMP-2 is an osteoinductive growth factor capable of inducing new bone formation in vivo. Although dosage studies using rhBMP-2 have been performed on species of lower phylogenetic level, they cannot be extrapolated to the primate. Dosage studies on nonhuman primates are essential before proceeding with human primate application. Methods. Six female adult Macaca mulatta (rhesus macaque) monkeys underwent an anterior L7-S1 interbody lumbar fusion. All six sites were assigned randomly to one of two fusion methods: 1) autogenous bone graft within a single freeze-dried smooth cortical dowel allograft cylinder (control) or 2) rhBMP-2-soaked absorbable collagen sponges within a single freeze-dried smooth cortical dowel allograft cylinder also soaked in rhBMP-2. The animals underwent a baseline computed tomography scan followed by 3- and 6-month postoperation scans. Anteroposterior and lateral radiographs of the lumbosacral spine were performed monthly. After the monkeys were killed, the lumbar spine fusionsites were evaluated. Histologic evaluation of all fusion sites was performed. Results. The three monkeys receiving rhBMP-2-soaked collagen sponges with a freeze-dried allograft demonstrated radiographic signs of fusion as early as 8 weeks. The control animals were slower to reveal new bone formation. The computed tomography scans revealed extensive fusion of the L7-S1 lumbar vertebrae in the group with rhBMP-2. A pseudarthrosis was present in two of the control animals. Conclusions. This study was able to document the efficacy of rhBMP-2 with an absorbable collagen sponge carrier and a cortical dowel allograft to promote anterior interbody fusion in a nonhuman primate model at a dose of 0.4 mg per implant site (1.5 mg/mL concentration). The rate of new bone formation and fusion with the use of rhBMP-2 and cortical dowel allograft appears to be far superior to that of autogenous cancellous iliac crest graft with cortical dowel allograft

Rapid mortality transition of Pacific Islands in the 19th century

The depopulation of Pacific islands during the 16th to 19th centuries is a striking example of historical mass mortality due to infectious disease. Pacific Island populations have not been subject to such cataclysmic infectious disease mortality since. Here we explore the processes which could have given rise to this shift in infectious disease mortality patterns. We show, using mathematical models, that the population dynamics exhibited by Pacific Island populations are unlikely to be the result of Darwinian evolution. We propose that extreme mortality during first-contact epidemics is a function of epidemiological isolation, not a lack of previous selection. If, as pathogens become established in populations, extreme mortality is rapidly suppressed by herd immunity, Pacific Island population mortality patterns can be explained with no need to invoke genetic change. We discuss the mechanisms by which this could occur, including (i) a link between the proportion of the population transmitting infectious agents and case-fatality rates, and (ii) the course of infection with pathogens such as measles and smallpox being more severe in adults than in children. Overall, we consider the present-day risk of mass mortality from newly emerging infectious diseases is unlikely to be greater on Pacific islands than in other geographical areas

Epistasis and the sensitivity of phenotypic screens for beta thalassaemia

Genetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The majority of affected births occur in low-income and lower-middle income countries. Screening programmes are a vital tool to counter these haemoglobinopathies by: (i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene-frequency estimates, to help ensure the optimal allocation of public health resources. For both of these functions it is vital that the screen performed is suitably sensitive. One popular first-stage screening option to detect carriers of beta thalassaemia in low-income countries is the One Tube Osmotic Fragility Test (OTOFT). Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the OTOFT in different epidemiological contexts. We demonstrate that interactions between the carrier states for beta thalassaemia and alpha thalassaemia, glucose-6-phosphate dehydrogenase deficiency and Southeast Asian Ovalocytosis have the potential to reduce the sensitivity of OTOFTs for beta thalassaemia heterozygosity to below 70%. Our results therefore caution against the widespread application of OTOFTs in regions where these erythrocyte variants co-occur

Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks.

BACKGROUND: Sickle haemoglobin (HbS) and haemoglobin C (HbC) are both caused by point mutations in the beta globin gene, and both offer substantial malaria protection. Despite the fact that the blood disorder caused by homozygosity for HbC is much less severe than that caused by homozygosity for HbS (sickle cell anaemia), it is the sickle mutation which has come to dominate many old-world malarious regions, whilst HbC is highly restricted in its geographical distribution. It has been suggested that this discrepancy may be due to sickle cell heterozygotes enjoying a higher level of malaria protection than heterozygotes for HbC. A higher fitness of sickle cell heterozygotes relative to HbC heterozygotes could certainly have allowed the sickle cell allele to spread more rapidly. However, observations that carrying either HbC or HbS enhances an individual's capacity to transmit malaria parasites to mosquitoes could also shed light on this conundrum. METHODS: A population genetic model was used to investigate the evolutionary consequences of the strength of malaria selection being correlated with either HbS frequency or HbC frequency. RESULTS: If the selection pressure from malaria is positively correlated with the frequency of either HbS or HbC, it is easier for HbS to succeed in the competitive interaction between the two alleles. CONCLUSIONS: A feedback process whereby the presence of variant haemoglobins increases the level of malaria selection in a population could have contributed to the global success of HbS relative to HbC, despite the former's higher blood disorder cost

Effective Screened Potentials of Strongly Coupled Semiclassical Plasma

The pseudopotentials of particle interaction of astrongly coupled semiclassical plasma, taking into account bothquantum-mechanical effects of diffraction at short distances andalso screening field effects at large distances are obtained. Thelimiting cases of potentials are considered.Comment: 15 pages, TeX, 7 figure

Detecting HLA-infectious disease associations for multi-strain pathogens

Human Leukocyte Antigen (HLA) molecules play a vital role helping our immune system to detect the presence of pathogens. Previous work to try and ascertain which HLA alleles offer advantages against particular pathogens has generated inconsistent results. We have constructed an epidemiological model to understand why this may occur. The model captures the epidemiology of a multi strain pathogen for which the host's ability to generate immunological memory responses to particular strains depends on that host's HLA genotype. We find that an HLA allele's ability to protect against infection, as measured in a case control study, depends on the population frequency of that HLA allele. Furthermore, our capability to detect associations between HLA alleles and infection with a multi strain pathogen may be affected by the properties of the pathogen itself (i.e R0 and length of infectious period). Both host and pathogen genetics must be considered in order to identify true HLA associations. However, in the absence of detailed pathogen genetic information, a negative correlation between the frequency of an HLA type and its apparent protectiveness against disease caused by multi strain pathogen is a strong indication that the HLA type in question is well adapted to a subset of strains of that pathogen

A module-based approach to foster and document the intercultural process before and during the residence abroad

This article contributes to the debate on what form of preparation and support can enhance the intercultural student experience during the Year Abroad. It presents a credit-bearing and multi-modal module at a UK university designed to both prepare students prior to departure through a series of workshops and activities on an e-portfolio and help them engage in meta-reflection on intercultural issues during their stay. The presentation of the curricular components of the course and instances extracted from student blogs are contextualised within theoretical considerations on intercultural education and a holistic approach to student development. The longitudinal evolution of the module is presented in the context of an iterative approach leading to a cycle of revisions and amendments. With its pragmatic stance this article aims to address one of the concerns recently expressed about intercultural education, namely that although intercultural theories are suitably incorporated in the latest thinking on communicative competence, there is a lack of evidence-based practice