A mathematical model for the dynamics and control of malaria in Nigeria.

Malaria is a life-threatening disease endemic in many African countries especially Nigeria. A mathematical model is used to study the dynamics of malaria in Nigeria. The model incorporates drug resistance, treatment, and the use of mosquito nets as preventive strategies. By fitting the model to data on the incidence of malaria in Nigeria, important parameters associated with the disease dynamics are estimated. Using these estimated parameters, the basic reproduction number is calculated, future dynamics simulated, and those parameters with a large impact on Nigerian malaria determined. Overall, the results indicate that the disease is likely to remain endemic in Nigeria unless better control measures are focused on the dominant resistant strain, treatment is improved and the use of mosquito nets become widespread.

High levels of fecundity in small and isolated populations of a self-compatible Aloe pollinated by opportunistic birds and bees.

Plant species that are effective colonisers of transient habitats are expected to have a capacity for uniparental reproduction and show flexibility in pollination systems. Such traits may enable populations to be established from a small number of founding individuals without these populations succumbing to reductions in fecundity arising from pollinator limitation. We tested these predictions for Aloe thraskii (Xanthorrhoeaceae), a succulent treelet that colonises shifting coastal dunes and has both bird and bee pollinators. We performed hand-pollination experiments, and selectively excluded bird visitors to determine differences in pollinator effectiveness. We measured pollinator visitation rates and fecundity in populations varying in their size, density and isolation distance. Controlled hand-pollinations revealed that unlike most other Aloe species, A. thraskii is self-compatible and thus capable of uniparental reproduction. The species does however depend on pollinators and is visited by various bird species as well as by bees. Fruit and seed set are not affected by selective exclusion of birds, thus indicating that bees are effective pollinators. Bird visitation rates increased with increasing plant height and population size, while bee visitation rates increased with increasing population size and density. We found that seed set per flower was lower in large populations than in small populations. These results suggest that establishment of populations of A. thraskii from a small number of individuals is unlikely to be limited by the fecundity of individual plants.

Effects of distance from models on the fitness of floral mimics.

Rewardless plants can attract pollinators by mimicking floral traits of rewarding heterospecific plants. This should result in the pollination success of floral mimics being dependent on the relative abundance of their models, as pollinator abundance and conditioning on model signals should be higher in the vicinity of the models. However, the attraction of pollinators to signals of the models may be partially innate, such that spatial isolation of mimics from model species may not strongly affect pollination success of mimics. We tested whether pollination rates and fruit set of the rewardless orchid Disa pulchra were influenced by proximity and abundance of its rewarding model species, Watsonia lepida. Pollination success of the orchid increased with proximity to the model species, while fruit set of the orchid increased with local abundance of the model species. Orchids that were experimentally translocated outside the model population experienced reduced pollinaria removal and increased pollinator-mediated self-pollination. These results confirm predictions that the pollination success of floral mimics should be dependent on the proximity and abundance of model taxa, and thus highlight the importance of ecological facilitation among species involved in mimicry systems.

Male interference with pollination efficiency in a hermaphroditic orchid.

Hermaphroditism can lead to both intra- and intersexual conflict between male and female gender functions. However, the effect that such gender conflicts have on pollination efficiency has seldom been investigated. By artificially reducing the number of available male gametes on an individual, we quantified whether male interference with pollination efficiency occurs in the self-compatible, moth-pollinated orchid Satyrium longicauda. We partially emasculated S. longicauda inflorescences and compared pollination success and fecundity in these plants to intact controls. Pollen in both groups of plants was colour-labelled so that its dispersal by pollinators could be tracked directly in the field. Intact flowers on partially emasculated inflorescences exported more pollen and received more cross-pollen and less self-pollen than those on intact inflorescences. Proportion of fruit set per plant was similar between the two treatments; however, fruits on partially emasculated plants had proportionally more viable seeds than those on intact controls. These results provide empirical evidence that male interference with pollination efficiency can occur in a hermaphroditic plant and that such interference can compromise fecundity. The most likely mechanism for such male interference is competition for placement on the proboscis of hawkmoth pollinators. Consequently, male competition for siring success may influence the evolution of sexual systems in hermaphroditic pollinator-dependent plants.

Effects of pollen reward removal on fecundity in a self-incompatible hermaphrodite plant.

The pollen of hermaphrodite plants is often utilised by flower-visiting animals. While pollen production has obvious benefits for plant male fitness, its consequences for plant female fitness, especially in self-incompatible hermaphrodite species, are less certain. Pollen production could either enhance seed production though increased pollinator attraction, or reduce it if ovules are discounted by deposition of self pollen, as can occur in species with late-acting self-incompatibility. To test the effects of pollen reward provision on female fitness, we artificially emasculated flowers in two populations of the succulent Aloe maculata (Asphodelaceae), which has a late-acting self-incompatibility system, over the course of its flowering period. Flowers of this species are visited by sunbirds (for nectar) and native bees (for pollen and nectar). We measured floral visitation rates, floral rejection rates, pollen deposition on stigmas and fruit and seed set in both emasculated and non-emasculated plants. We found that flowers of emasculated plants suffered reduced visitation and increased rejection (arrival without visitation) by bees, but not by sunbirds; had fewer pollen grains deposited on stigmas and showed an overall decrease in fruit set and seed set. Rates of seed abortion were, however, greatly reduced in emasculated flowers. This study shows that pollen rewards can be important for seed set, even in self-incompatible plants, which have been assumed to rely on nectar rewards for pollinator attraction. Seed abortion was, however, increased by pollen production, a result that highlights the complexity of selection on pollen production in hermaphrodite flowers.

Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis.

High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalenesulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC(50) values in the region of 1-20 nM.

Natural DNA mixtures generated in fraternal twins in utero.

Analysis of multiple genetic loci using short tandem repeats (STR) is widely used in human identity testing because the extensive polymorphism at these loci allows for a high degree of discrimination among individuals. We recently received a forensic case that included several pieces of evidence and reference blood samples. Upon initial testing, one of the suspects had a DNA profile that included three alleles at four of the nine loci tested (vWA, FGA, TH01, and D5S818). At each locus, two of the alleles appeared to be "major" alleles with a third "minor" allele present. The profile appeared to be a mixture of two people. Contamination of this first reference sample was suspected and a second, unopened blood specimen was requested from this individual. The DNA profile from this second reference specimen was identical to that of the original specimen at each locus. One of the evidence samples also displayed an identical mixed DNA profile matching that of the reference specimens mentioned above. The relative peak heights of the two "major" and one "minor" allele remained constant in all three samples. Additional background information revealed that the suspect had not received a bone marrow transplant or blood transfusion. However, it was disclosed that this individual is a fraternal (dizygotic) twin. We hypothesize that an exchange of blood cells between the fetuses occurred in utero and that the additional alleles present in these reference samples are derived from cells contributed by his twin sibling. No additional specimens from the suspect or his twin could be obtained for confirmation, and our hypothesis remains untested. Forensic scientists should be aware of this possibility when faced with a DNA profile in which extra alleles at multiple loci are detected.

Loss of heterozygosity detected in a short tandem repeat (STR) locus commonly used for human DNA identification.

Short tandem repeat (STR) markers are commonly used in basic genetic research and in human identification testing. Clinically, STRs can be used to study genetic alterations in tumors. A genetic deletion common to many types of cancer is referred to as the loss of heterozygosity (LOH). Numerous examples of LOH in cancer have been described and some have been mapped to areas located in close proximity to markers employed in human identity testing. Despite this fact, LOH has rarely been observed for STR loci commonly employed in forensic testing. Recently, for medico-legal purposes, we were asked to determine whether a tissue biopsy originated from a particular individual. For a reference source we assessed two specimens, one from normal tissue and one from cancerous tissue. When both reference specimens were used to generate DNA profiles, we observed LOH at one STR locus, D13S317. As demonstrated in other cancers only the cancerous biopsy demonstrated LOH. The forensic community should be cognizant of these unusual circumstances because, as identification of human DNA continues to be used more extensively, certain instances will arise in which reference material will not be readily available. In these situations, archived specimens may be employed as a reference source. Clinical specimens such as tissue biopsies should be used with caution if they have not been confirmed to contain normal tissue.

Design and synthesis of diaminopyrrolidinone inhibitors of human osteoclast cathepsin K.

The structure-based design and synthesis of lactam-constrained azapeptide inhibitors of human cathepsin K are described. Enhanced stability to proteolytic cleavage over acyclic analogues is discussed.

Residence time calculation for chemotactic bacteria within porous media.

Local chemical gradients can have a significant impact on bacterial population distributions within subsurface environments by evoking chemotactic responses. These local gradients may be created by consumption of a slowly diffusing nutrient, generation of a local food source from cell lysis, or dissolution of nonaqueous phase liquids trapped within the interstices of a soil matrix. We used a random walk simulation algorithm to study the effect of a local microscopic gradient on the swimming behavior of bacteria in a porous medium. The model porous medium was constructed using molecular dynamics simulations applied to a fluid of equal-sized spheres. The chemoattractant gradient was approximated with spherical symmetry, and the parameters for the swimming behavior of soil bacterium Pseudomonas putida were based on literature values. Two different mechanisms for bacterial chemotaxis, one in which the bacteria responded to both positive and negative gradients, and the other in which they responded only to positive gradients, were compared. The results of the computer simulations showed that chemotaxis can increase migration through a porous medium in response to microscopic-scale gradients. The simulation results also suggested that a more significant role of chemotaxis may be to increase the residence time of the bacteria in the vicinity of an attractant source.

Turn angle and run time distributions characterize swimming behavior for Pseudomonas putida.

The swimming behavior of Pseudomonas putida was analyzed with a tracking microscope to quantify its run time and turn angle distributions. Monte Carlo computer simulations illustrated that the bimodal turn angle distribution of P. putida reduced collisions with obstacles in porous media in comparison to the unimodal distribution of Escherichia coli.

Random walk calculations for bacterial migration in porous media.

Bacterial migration is important in understanding many practical problems ranging from disease pathogenesis to the bioremediation of hazardous waste in the environment. Our laboratory has been successful in quantifying bacterial migration in fluid media through experiment and the use of population balance equations and cellular level simulations that incorporate parameters based on a fundamental description of the microscopic motion of bacteria. The present work is part of an effort to extend these results to bacterial migration in porous media. Random walk algorithms have been used successfully to date in nonbiological contexts to obtain the diffusion coefficient for disordered continuum problems. This approach has been used here to describe bacterial motility. We have generated model porous media using molecular dynamics simulations applied to a fluid with equal sized spheres. The porosity is varied by allowing different degrees of sphere overlap. A random walk algorithm is applied to simulate bacterial migration, and the Einstein relation is used to calculate the effective bacterial diffusion coefficient. The tortuosity as a function of particle size is calculated and compared with available experimental results of migration of Pseudomonas putida in sand columns. Tortuosity increases with decreasing obstacle diameter, which is in agreement with the experimental results.

Nutritional parameters in urban and rural Zulus.

Anthropometric, biochemical and haematological nutritional parameters were measured in 103 (65 men, 38 women) Durban Zulu adults (urban) and 109 (41 men, 68 women) Tugela Ferry Zulu adults (rural). Men conformed to an ideal weight for height whereas women were 18% overweight in Tugela Ferry and 30% so in Durban. Mean arm muscle circumference in men was between the 10th and 20th centiles. Other nutritional parameters were similar to those accepted internationally as normal. In particular the serum albumin level was normal in both urban and rural Zulus. There was little change in the parameters with age except that hand grip as measured by dynamometry fell with age (P less than 0,05). Serum albumin levels fell with age in women (P less than 0,01) but not in men. Nine mothers of babies suffering from kwashiorkor showed normal nutritional profiles.

Nutritional assessment by hand grip dynamometry.

Hand grip dynamometry was studied in 109 normally nourished and 26 malnourished patients. The grip strength was 37,5 +/- 9,9 kg/m2 in normal men, 30,5 +/- 14,4 kg/m2 in men with carcinoma of the oesophagus (starvation-adapted) and 22,0 +/- 9,2 kg/m2 in catabolic men (P less than 0,001). Normal women had a grip strength of 31,6 +/- 7,5 kg/m2 compared with 22,3 +/- 7,0 in catabolic women (P = 0,083). Hand grip dynamometry fell with age (r = 0,69 men; r = 0,57 women), although the correlation was only statistically significant in women (P less than 0,05). There was a strong correlation between right and left hand grip (r = 0,84 men; r = 0,86 women), but hand grip did not correlate well with other indices of nutritional status. Although hand grip dynamometry is a quick, easy and reproducible test, and grip strength is reduced in malnutrition, it cannot replace other tests of nutritional status.