Estimating and Mapping the Population at Risk of Sleeping Sickness

Background

Human African trypanosomiasis (HAT), also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries. Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy. Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from “very high” to “very low,” and to estimate the corresponding at-risk population.

Results

Approximately 70 million people distributed over a surface of 1.55 million km² are estimated to be at different levels of risk of contracting HAT. Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense. Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported.

Discussion

Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population. Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population. By contrast, it will be possible to explore trends in the future. The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness.     

Phylogeographic patterns of decapod crustaceans at the Atlantic-Mediterranean transition

Comparative multispecies studies allow contrasting the effect of past and present oceanographic processes on phylogeographic patterns. In the present study, a fragment of the COI gene was analyzed in seven decapod crustacean species from five families and with different bathymetric distributions. A total of 769 individuals were sampled along the Atlantic-Mediterranean transition area in order to test the effect of three putative barriers to gene flow: Strait of Gibraltar, Almeria-Oran Front and Ibiza Channel. A significant effect of the Strait of Gibraltar was found in the crabs Liocarcinus depurator and Macropipus tuberculatus. The Ibiza Channel had a significant effect for L. depurator. However, the Almeria-Oran front was not found to have a significant effect on any of the studied species. Higher levels of population structure were found in shallow-water species, although the number of species sampled should be increased to obtain a conclusive pattern. The haplotypes within the different species coalesced at times that could be related with past climatic events occurring before, during and after the last glacial maximum. Given the large diversity of phylogeographic patterns obtained within decapods, it is concluded that both historical and contemporary processes (marine current patterns, bathymetry and life-history traits) shape the phylogeographic patterns of these crustaceans.     

New insights into social and space use behaviour of the endangered Pyrenean desman (<Emphasis Type="Italic">Galemys pyrenaicus</Emphasis>)

We describe novel aspects of the social organisation of the Pyrenean desman, Galemys pyrenaicus, by studying home range and shelter use behaviour in a local population. A total of 45 individuals were trapped of which 20 provided informative radiotracking data. In contrast to the currently accepted hypothesis [Stone RD. The social organization of the Pyrenean desman (Galemys pyrenaicus) as revealed by radiotelemetry. J Zool 212:117–129; 1987b; Stone RD, Gorman ML. Social organization of the European mole (Talpa europaea) and the Pyrenean desman (Galemys pyrenaicus). Mammal Rev 15 (1):35–42; 1985] individuals were not strictly territorial. Notably, there was no aggression between conspecifics, with simultaneous use of resting sites (shelters used for more than one hour). Resting sites were not permanent or exclusive for any individual. Individuals shared resting sites simultaneously, regardless of sex or age. Our observations recall for a new evaluation of the social structure and organisation of this species based on the new evidence that reveals higher frequency of social interactions than previously described. Resting sites may play an important role in the social organisation of the species, for instance by allowing direct and indirect communicative interactions among neighbouring individuals. This finding is of significance for the management (e.g. census and population monitoring) and conservation (e.g. habitat suitability to allow social interactions) of this endemic and seriously threatened unique mammal.     

Lack of fitness costs of insecticide resistance in the western flower thrips (Thysanoptera: Thripidae)

The fitness costs of spinosad and acrinathrin resistance was investigated in the western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae). Fitness studies were conducted on susceptible and resistant strains of F. occidentalis. Resistant females were significantly more fecund (number of eggs per female) than susceptible females. The hatching rate (fertility) for both susceptible and acrinathrin-resistant strains was significantly lower than in the spinosad-resistant strain. Mean developmental time from egg to adult did not differ between thrips populations. Similarly, female longevity did not differ between populations. These data suggest that lack of fitness costs related to insecticide resistance may accelerate the development of insecticide resistance in populations of F. occidentalis from southeastern Spain.     

Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice

T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice. TCR transgenic mice with CD8(+) T cells specific for IGRP(206-214) (NOD8.3 mice) develop accelerated diabetes that requires CD4(+) T cell help. We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand. In this study, we show that diabetes development is dramatically reduced in NOD8.3 mice crossed to NOD mice tolerant to proinsulin (NOD-PI mice). This indicates that immunity to proinsulin is even required in the great majority of NOD8.3 mice that have a pre-existing repertoire of IGRP(206-214)-specific cells. However, protection from diabetes could be overcome by inducing islet inflammation either by a single dose of streptozotocin or anti-CD40 agonist Ab treatment. This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.     

A dynamic view of enzyme catalysis

Recent experimental advances have shown that enzymes are flexible molecules, and point to a direct link between dynamics and catalysis. Movements span a wide time range, from nano- to milli-seconds. In this paper we introduce two aspects of enzyme flexibility that are treated with two appropriate techniques. First, transition path sampling is used to obtain an unbiased picture of the transition state ensemble in chorismate mutase, as well as its local flexibility and the energy flow during the chemical step. Second, we consider the binding and release of substrates in L-rhamnulose-1-phosphate aldolase. We have calculated the normal modes of the enzyme with the elastic network model. The lowest frequency modes generate active site deformations that change the coordination number of the catalytic zinc ion. The coordination lability of zinc allows the binding and release of substrates. Substitution of zinc by magnesium blocks the exchange of ligands. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Purinergic and nitrergic junction potential in the human colon

The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 microM), but not the P2Y receptor agonist adenosine 5'-O-2-thiodiphosphate (10 microM), was able to cause a sustained relaxation. NG-nitro-L-arginine (L-NNA) (1 mM), a NO synthase inhibitor, but not 2'-deoxy-N6-methyl adenosine 3',5'-diphosphate tetraammonium salt (MRS 2179) (10 microM), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 microM). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1 mM), hexamethonium (100 microM), MRS 2179 (1 microM), and NF023 (10 microM). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).     

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.     

Stability of spinosad resistance in Frankliniella occidentalis (Pergande) under laboratory conditions

The stability of spinosad resistance in western flower thrips (WFT), Frankliniella occidentalis (Pergande), populations with differing initial frequencies of resistance was studied in laboratory conditions. The stability of resistance was assessed in bimonthly residual bioassays in five populations with initial frequencies of 100, 75, 50, 25 and 0% of resistant individuals. There were no consistent changes in susceptibility of the susceptible strain after eight months without insecticide pressure. In the resistant strain, very highly resistant to spinosad (RF50>23,000-fold), resistance was maintained up to eight months without further exposure to spinosad. In the absence of any immigration of susceptible genes into the population, resistance was stable. In the case of the population with different initial frequency of resistant thrips, spinosad resistance declined significantly two months later in the absence of selection pressure. With successive generations, these strains did not change significantly in sensitivity. Spinosad resistance in F. occidentalis declined significantly in the absence of selection pressure and the presence of susceptible WFT. These results suggest that spinosad resistance probably is unstable under field conditions, primarily due to the immigration of susceptible WFT. Factors influencing stability or reversion of spinosad resistance are discussed.