Plasticity in transmission strategies of the malaria parasite, Plasmodium chabaudi : environmental and genetic effects

Parasites may alter their behaviour to cope with changes in the within-host environment. In particular, investment in transmission may alter in response to the availability of parasite resources or host immune responses. However, experimental and theoretical studies have drawn conflicting conclusions regarding parasites' optimal (adaptive) responses to deterioration in habitat quality. We analyse data from acute infections with six genotypes of the rodent malaria species to quantify how investment in transmission (gametocytes) is influenced by the within-host environment. Using a minimum of modelling assumptions, we find that proportional investment in gametocytogenesis increases sharply with host anaemia and also increases at low parasite densities. Further, stronger dependence of investment on parasite density is associated with greater virulence of the parasite genotype. Our study provides a robust quantitative framework for studying parasites' responses to the host environment and whether these responses are adaptive, which is crucial for predicting the short-term and evolutionary impact of transmission-blocking treatments for parasitic diseases

The ecology of nasal colonization of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus: the role of competition and interactions with host's immune response

<p>Abstract</p> <p>Background</p> <p>The first step in invasive disease caused by the normally commensal bacteria <it>Streptococcus pneumoniae</it>, <it>Staphylococcus aureus </it>and <it>Haemophilus influenzae </it>is their colonization of the nasal passages. For any population to colonize a new habitat it is necessary for it to be able to compete with the existing organisms and evade predation. In the case of colonization of these species the competition is between strains of the same and different species of bacteria and the predation is mediated by the host's immune response. Here, we use a neonatal rat model to explore these elements of the ecology of nasal colonization by these occasionally invasive bacteria.</p> <p>Results</p> <p>When neonatal rats are colonized by any one of these species the density of bacteria in the nasal passage rapidly reaches a steady-state density that is species-specific but independent of inoculum size. When novel populations of <it>H. influenzae </it>and <it>S. pneumoniae </it>are introduced into the nasal passages of neonatal rats with established populations of the same species, residents and invaders coexisted. However, this was not the case for <it>S. aureus </it>- the established population inhibited invasion of new <it>S. aureus </it>populations. In mixed-species introductions, <it>S. aureus </it>or <it>S. pneumoniae </it>facilitated the invasion of another <it>H. influenzae </it>population; for other pairs the interaction was antagonistic and immune-mediated. For example, under some conditions <it>H. influenzae </it>promoted an immune response which limited the invasion of <it>S. pneumoniae</it>.</p> <p>Conclusions</p> <p>Nasal colonization is a dynamic process with turnover of new strains and new species. These results suggest that multiple strains of either <it>H. influenzae </it>or <it>S. pneumoniae </it>can coexist; in contrast, <it>S. aureus </it>strains require a host to have no other <it>S. aureus </it>present to colonize. Levels of colonization (and hence the possible risk of invasive disease) by <it>H. influenzae </it>are increased in hosts pre-colonized with either <it>S. aureus </it>or <it>S. pneumoniae</it>.</p

A Sterile 20 Family Kinase and Its Co-factor CCM-3 Regulate Contractile Ring Proteins on Germline Intercellular Bridges

Germ cells in most animals are connected by intercellular bridges, actin-based rings that form stable cytoplasmic connections between cells promoting communication and coordination [1]. Moreover, these connections are required for fertility [1, 2]. Intercellular bridges are proposed to arise from stabilization of the cytokinetic ring during incomplete cytokinesis [1]. Paradoxically, proteins that promote closure of cytokinetic rings are enriched on stably open intercellular bridges [1, 3, 4]. Given this inconsistency, the mechanism of intercellular bridge stabilization is unclear. Here, we used the C. elegans germline as a model for identifying molecular mechanisms regulating intercellular bridges. We report that bridges are actually highly dynamic, changing size at precise times during germ cell development. We focused on the regulation of bridge stability by anillins, key regulators of cytokinetic rings and cytoplasmic bridges [1, 4-7]. We identified GCK-1, a conserved serine/threonine kinase [8], as a putative novel anillin interactor. GCK-1 works together with CCM-3, a known binding partner [9], to promote intercellular bridge stability and limit localization of both canonical anillin and non-muscle myosin II (NMM-II) to intercellular bridges. Additionally, we found that a shorter anillin, known to stabilize bridges [4, 7], also regulates NMM-II levels at bridges. Consistent with these results, negative regulators of NMM-II stabilize intercellular bridges in the Drosophila egg chamber [10, 11]. Together with our findings, this suggests that tuning of myosin levels is a conserved mechanism for the stabilization of intercellular bridges that can occur by diverse molecular mechanisms

Improving Confidence in Crystal Structure Solutions Using NMR Crystallography: The Case of β-Piroxicam

NMR crystallographic techniques are used to validate a structure of β-piroxicam determined from powder X-ray diffraction (PXRD) with a relatively poor R-factor. Geometry optimization of PXRD- and single-crystal XRD- derived structures results in convergence to the same energy of the structures, with minimal atomic displacements, and good agreement of gauge-included projector augmented wave (GIPAW) calculated and experimentally determined NMR 1H, 13C, and 15N chemical shifts, and 14N quadrupolar parameters. Calculations on isolated molecules combined with 2D magic-angle spinning (MAS) 1H double-quantum (DQ) and 14N–1H NMR experiments confirm the 3D packing arrangement of β-piroxicam. NMR crystallography is shown to be an effective means of validating crystal structures that might otherwise be considered sceptically on the basis of diffraction data alone

protein complexes

Mass spectrometry-based shotgun proteomic analysis of C. elegan

Predicting the critical density of topological defects in O(N) scalar field theories

O(N) symmetric $\lambda \phi^4$ field theories describe many critical phenomena in the laboratory and in the early Universe. Given N and $D\leq 3$, the dimension of space, these models exhibit topological defect classical solutions that in some cases fully determine their critical behavior. For N=2, D=3 it has been observed that the defect density is seemingly a universal quantity at T_c. We prove this conjecture and show how to predict its value based on the universal critical exponents of the field theory. Analogously, for general N and D we predict the universal critical densities of domain walls and monopoles, for which no detailed thermodynamic study exists. This procedure can also be inverted, producing an algorithm for generating typical defect networks at criticality, in contrast to the canonical procedure, which applies only in the unphysical limit of infinite temperature.Comment: 4 pages, 3 figures, uses RevTex, typos in Eq.(11) and (14) correcte

Resource selection of deer hunters in Georgia\u27s Appalachian Mountains

White‐tailed deer (Odocoileus virginianus) and hunters on 2 Wildlife Management Areas (WMAs) within the Chattahoochee National Forest of northern Georgia, USA, significantly declined in number from the 1980s to 2018. Managers were interested in understanding how they could manipulate hunter distribution according to deer management goals. To understand the spatial distribution of hunting pressure and factors driving hunter resource selection, we analyzed GPS tracking data from 58 deer hunters over the 2018–2019 and 2019–2020 hunting seasons. We evaluated hunter selection on 3 spatial scales relative to elevation, slope, and distance from roads, trails, wildlife openings, deciduous forest, mixed forest, and evergreen forest. We incorporated covariates into 6 binary logistic regression models, plus a null model, within a used versus available framework. First, we compared hunter locations to available locations generated within the 2 WMAs. Elevation and distance to deciduous forest had the greatest effect on hunter selection, where hunters selected for lower elevations and closer proximity to deciduous forest. Second, we compared individual hunting bout locations to available locations generated within a buffer around the hunter\u27s starting location with a buffer radius equal to the maximum distance they travelled from their starting location. At the bout scale, distance to wildlife openings and elevation were the most important drivers of hunter selection; hunters selected areas closer to wildlife openings and higher elevations. Third, we compared individual hunter stand locations (used) to randomly selected locations along the hunter\u27s travel path (available). Only distance to roads and deciduous forest were significant in explaining hunter selection of stands. Hunters chose locations farther from roads and closer to deciduous forest relative to their travel paths. Mapping our WMA‐scale results revealed that only 5% of the total WMA area contained a greater relative probability of hunter selection compared to the probability of non‐selection. Our results suggest that vast refuge areas for deer likely existed on the WMAs during our study period. Manipulating hunter distribution is not necessary to aid in sustaining deer on either WMA at this time

White-tailed deer (\u3ci\u3eOdocoileus virginianus\u3c/i\u3e) fawn survival and the influence of landscape characteristics on fawn predation risk in the Southern Appalachian Mountains, USA

In the Southern Appalachian region of the United States, harvest data has indicated the occurrence of low deer densities while exposing a trend of declining white-tailed deer (Odocoileus virginianus) populations over the past several decades in northern Georgia. A triumvirate of increasing fawn predator populations reside in the Southern Appalachian Mountains including coyotes (Canis latrans), black bears (Ursus americanus) and bobcats (Lynx rufus). This region is also characterized by a homogenous landscape composed of mature forests and sparse understory vegetation, likely lacking adequate cover to offer fawns refugia from predators. Our objectives were to estimate survival and cause-specific mortality rates of fawns while assessing a possible link between mortality risk, intrinsic fawn characteristics (i.e., birth mass, Julian birth date, sibling status), and landscape features within fawn usage areas. During 2018–2020, we radio-collared 71 fawns within the Chattahoochee National Forest of northern Georgia, USA and monitored survival to 12 weeks of age. We observed low fawn survival (cumulative = 0.157, 95% CI = 0.091–0.273; vaginal implant transmitter = 0.196, 95% CI = 0.096–0.403) with predation as the leading cause of all known mortalities (45 of 55 mortalities; 82%) due primarily to coyotes (n = 22), black bears (n = 12), and bobcats (n= 7). Relationships between landscape features and fawn predation risk were minimal with only one informative covariate. Increasing amounts of early successional land cover within fawn usage areas decreased fawn mortality risk within the first 20 days of life, but elevated mortality risk thereafter. All fawns with any amount of early successional land cover in their usage areas died of predation (n = 13) at various time intervals, suggesting limited areas of potential fawning cover may be targeted by predators. However, fawn predation risk seemed to be high regardless of landscape covariates due to the limited number of surviving fawns. Coyote-caused mortality occurred over a longer period at a consistently higher magnitude than all other forms of mortality, indicating possible delayed prey-switching behavior and coyote predation as an important factor of fawn survival. The low recruitment of fawns influenced by high predation rates and homogenous habitat conditions is likely the cause of deer population declines in the region