A High Force of Plasmodium vivax Blood-Stage Infection Drives the Rapid Acquisition of Immunity in Papua New Guinean Children

Background

When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax (_molFOB, i.e. the number of genetically distinct blood-stage infections over time), and compared it to previously reported values for P. falciparum.

Methods

P. vivax _molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1–4.5 years.

Results

On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with _molFOB (incidence rate ratio (IRR) = 1.99, 95% confidence interval (CI95) [1.80, 2.19]), _molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001) compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02).

Conclusion

P. vivax _molFOB is considerably higher than P. falciparum _molFOB (5.5 clones/child/year-at-risk). The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.     

Rational design of the survivin/CDK4 complex by combining protein–protein docking and molecular dynamics simulations

Survivin, the smallest inhibitor of apoptosis protein (IAP), is a valid target for cancer research. It mediates both the apoptosis pathway and the cell cycle and has been proposed to form a complex with the cyclin-dependent kinase protein CDK4. The resulting complex transports CDK4 from the cytosol to the nucleus, where CDK4 participates in cell division. Survivin has been recognized as a node protein that interacts with several partners; disruption of the formed complexes can lead to new anticancer compounds. We propose a rational model of the survivin/CDK4 complex that fulfills the experimental evidence and that can be used for structure-based design of inhibitors modifying its interface recognition. In particular, the suggested complex involves the alpha helical domain of survivin and resembles the mode of binding of survivin in the survivin/borealin X-ray structure. The proposed model has been obtained by combining protein–protein docking, fractal-based shape complementarity, electrostatics studies and extensive molecular dynamics simulations.

Cu3P Binary Phosphide: Synthesis via a Wet Mechanochemical Method and Electrochemical Behavior as Negative Electrode Material for Lithium‐Ion Batteries

Mechanochemical synthesis of Cu₃P in the presence of n‐dodecane results in a material with a secondary particle size distribution of 10 μm, secondary particles which consist of homogeneously agglomerated 20 nm primary particles. The electrochemical performance of Cu₃P with lithium is influenced by the reaction depth, in other words by the lower potential cut‐off. During the electrochemical reaction, the displacement of copper by lithium from the Cu₃P structure until the formation of Li₃P and Cu deteriorates the capacity retention. Improved performance was obtained when the charge potential was limited to 0.50 V (vs. Li/Li⁺) and the formation of the Li_xCu_3‐xP phase (0 ≤ × ≤ 2). In this case, when the potential is limited to 0.5 V, the capacity is stable for more than 50 cycles. Acceptable electrochemical performances in Li‐ion cells within the voltage range 0.50–2.0 V (vs. Li/Li⁺) were shown when Cu₃P was used as an anode and Li_1.2(Ni_0.13Mn_0.54Co_0.13)O₂ and LiNi_0.5Mn_1.5O₄ as positive electrode materials.     

Effects of post-thaw incubation on motility,acrosomal integrity and in vitro fertilizing capacity of boar spermatozoa cryopreserved in 0.5 and 5 ml straws

The effect of post-thaw incubation (0 vs. 5 h at 15 °C) and straw size (5 vs. 0.5 ml) on motility, acrosomal integrity and in vitro fertilizing (IVF) capacity of cryopreserved boar spermatozoa was studied. In samples assessed immediately after thawing, no differences were found between the two straw sizes. After 5 h post-thaw incubation, all parameters, except polyspermy, decreased and, spermatozoa packaged in 5 ml straws showed better functional and IVF parameters than these in 0.5 ml straws.     

Road-associated edge effects in Amazonia change termite community composition by modifying environmental conditions

Roads and road-building are among the most important environmental impacts on forests near urban areas, but their effects on ecosystem processes and species distributions remain poorly known. Termites are the primary decomposer organisms in tropical forests and their spatial distribution is strongly affected by vegetation and soil structure. We studied the impacts of road construction on termite community structure in an Amazonian forest fragment near Manaus, Brazil. One leading question was whether the fragment under study was large enough to maintain the termite species pool present in nearby continuous forests. We also asked how soil moisture and canopy openness varied with proximity to roads, and whether these changes were associated with changes in termite species richness and composition in the fragment. While the forest fragment had a termite composition very similar to that of continuous forests, roads caused important changes in soil moisture and canopy openness, especially when close to forest edges. At distances of up to 81 m from roads, changes in soil moisture were significantly related to changes in termite species composition, but there was no correlation between canopy openness and species richness or composition. These results suggest that fragmentation caused by roads impacts termites in a different and less damaging manner than fragmentation caused by other kinds of degradation, and that even fragments bisected by roads can support very diverse communities and even undescribed taxa of termites. We conclude that a buffer zone should be established for conservation purposes in the reserves surrounded by roads.     

Folding Pathways of a Knotted Protein with a Realistic Atomistic Force Field

We report on atomistic simulation of the folding of a natively-knotted protein, MJ0366, based on a realistic force field. To the best of our knowledge this is the first reported effort where a realistic force field is used to investigate the folding pathways of a protein with complex native topology. By using the dominant-reaction pathway scheme we collected about 30 successful folding trajectories for the 82-amino acid long trefoil-knotted protein. Despite the dissimilarity of their initial unfolded configuration, these trajectories reach the natively-knotted state through a remarkably similar succession of steps. In particular it is found that knotting occurs essentially through a threading mechanism, involving the passage of the C-terminal through an open region created by the formation of the native -sheet at an earlier stage. The dominance of the knotting by threading mechanism is not observed in MJ0366 folding simulations using simplified, native-centric models. This points to a previously underappreciated role of concerted amino acid interactions, including non-native ones, in aiding the appropriate order of contact formation to achieve knotting.