Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

<p>Abstract</p> <p>Background</p> <p>In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease.</p> <p>Methods</p> <p>Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP). Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined.</p> <p>Results</p> <p>We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease) and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8) vs. 11.4 (9.2-12.2), P = 0.032), ADP (1.6 (1.2-2.1) vs. 2.6 (1.9-3.5), P = 0.002) and CRP (9.2 (8.5-10.8) vs. 11.5 (9.5-12.9), P = 0.004). Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups.</p> <p>Conclusion</p> <p>In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.</p

Gravitational Waves from Gravitational Collapse

Gravitational wave emission from the gravitational collapse of massive stars has been studied for more than three decades. Current state of the art numerical investigations of collapse include those that use progenitors with realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non--axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Impact of Age and Comorbidity on Choice and Outcome of Two Different Treatment Options for Patients with Potentially Curable Esophageal Cancer

Purpose. This study was designed to assess the impact of age and comorbidity on choice and outcome of definitive chemoradiotherapy (dCRT) or neoadjuvant chemoradiotherapy plus surgery. Methods. In this population-based study, all patients with potentially curable EC (cT1N?/cT2-3, TX, any cN, cM0) diagnosed in the South East of the Netherlands between 2004 and 2014 were included. Kaplan–Meier method with log-rank tests and multivariable Cox regression analysis were used to compare overall survival (OS). Results. A total of 702 patients was included. Age C 75 years and multiple comorbidities were associated with a higher probability for dCRT (odds ratio [OR] 8.58; 95% confidence interval [CI] 4.72–15.58; and OR 3.09; 95% CI 1.93–4.93). The strongest associations were found for the combination of hypertension plus diabetes (OR 3.80; 95% CI 1.97–7.32) and the combination of cardiovascular with pulmonary comorbidity (OR 3.18; 95% CI 1.57–6.46). Patients with EC who underwent dCRT had a poorer prognosis than those who underwent nCRT plus surgery, irrespective of age, number, and type of comorbidities. In contrast, for patients with squamous cell carcinoma with C 2 comorbidities or age C 75 years, OS was comparable between both groups (hazard ratio [HR] 1.52; 95% CI 0.78–2.97; and HR 0.73; 95% CI 0.13–4.14). Conclusions. Histological tumor type should be acknowledged in treatment choices for patients with esophageal cancer. Neoadjuvant chemoradiotherapy plus surgery should basically be advised as treatment of choice for operable esophageal adenocarcinoma patients. For patients with esophageal squamous cell carcinoma with C 2 comorbidities or age C 75 years, dCRT may be the preferred strategy

The effects of warming on the ecophysiology of two co-existing kelp species with contrasting distributions

The northeast Atlantic has warmed significantly since the early 1980s, leading to shifts in species distributions and changes in the structure and functioning of communities and ecosystems. This study investigated the effects of increased temperature on two co-existing habitat-forming kelps: Laminaria digitata, a northern boreal species, and Laminaria ochroleuca, a southern Lusitanian species, to shed light on mechanisms underpinning responses of trailing and leading edge populations to warming. Kelp sporophytes collected from southwest United Kingdom were maintained under 3 treatments: ambient temperature (12 °C), +3 °C (15 °C) and +6 °C (18 °C) for 16 days. At higher temperatures, L. digitata showed a decline in growth rates and Fv/Fm, an increase in chemical defence production and a decrease in palatability. In contrast, L. ochroleuca demonstrated superior growth and photosynthesis at temperatures higher than current ambient levels, and was more heavily grazed. Whilst the observed decreased palatability of L. digitata held at higher temperatures could reduce top-down pressure on marginal populations, field observations of grazer densities suggest that this may be unimportant within the study system. Overall, our study suggests that shifts in trailing edge populations will be primarily driven by ecophysiological responses to high temperatures experienced during current and predicted thermal maxima, and although compensatory mechanisms may reduce top-down pressure on marginal populations, this is unlikely to be important within the current biogeographical context. Better understanding of the mechanisms underpinning climate-driven range shifts is important for habitat-forming species like kelps, which provide organic matter, create biogenic structure and alter environmental conditions for associated communities

Does urbanization explain differences in interactions between an insect herbivore and its natural enemies and mutualists?

Urbanization can alter the composition of arthropod communities. However, little is known about how urbanization affects ecological interactions. Using experimental colonies of the black bean aphid Aphis fabae Scopoli reared on Vicia faba L, we asked if patterns of predator-prey, host-parasitoid and ant-aphid mutualisms varied along an urbanization gradient across a large town in southern England. We recorded the presence of naturally occurring predators, parasitoid wasps and mutualistic ants together with aphid abundance. We examined how biotic (green areas and plant richness) and abiotic features (impervious surfaces and distance to town center) affected (1) aphid colony size, (2) the likelihood of finding predators, mutualistic ants and aphid mummies (indicating the presence of parasitoids), and (3) how the interplay among these factors affected patterns of parasitoid attack, predator abundance, mutualistic interactions and aphid abundance. The best model to predict aphid abundance was the number of mutualistic ants attending the colonies. Aphid predators responded negatively to both the proportion of impervious surfaces and to the number of mutualistic ants farming the colonies, and positively to aphid population size, whereas parasitized aphids were found in colonies with higher numbers of aphids and ants. The number of mutualistic ants attending was positively associated with aphid colony size and negatively with the number of aphid predators. Our findings suggest that for insect-natural enemy interactions, urbanization may affect some groups, while not influencing others, and that local effects (mutualists, host plant presence) will also be key determinants of how urban ecological communities are formed

Role of Synucleins in Alzheimer’s Disease

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-β protein (Aβ) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of α-synuclein (α-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Aβ and Tau; however, recent studies suggest that α-syn might also play a role in the pathogenesis of AD. For example, fragments of α-syn can associate with amyloid plaques and Aβ promotes the aggregation of α-syn in vivo and worsens the deficits in α-syn tg mice. Moreover, α-syn has also been shown to accumulate in limbic regions in AD, Down’s syndrome, and familial AD cases. Aβ and α-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Aβ and α-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Aβ and α-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Large grazers modify effects of aboveground–belowground interactions on small-scale plant community composition

Aboveground and belowground organisms influence plant community composition by local interactions, and their scale of impact may vary from millimeters belowground to kilometers aboveground. However, it still poorly understood how large grazers that select their forage on large spatial scales interact with small-scale aboveground–belowground interactions on plant community heterogeneity. Here, we investigate how cattle (Bos taurus) modify the effects of interactions between yellow meadow ants (Lasius flavus) and European brown hares (Lepus europaeus) on the formation of small-scale heterogeneity in vegetation composition. In the absence of cattle, hares selectively foraged on ant mounds, while under combined grazing by hares and cattle, vertebrate grazing pressure was similar on and off mounds. Ant mounds that were grazed by only hares had a different plant community composition compared to their surroundings: the cover of the grazing-intolerant grass Elytrigia atherica was reduced on ant mounds, whereas the relative cover of the more grazing-tolerant and palatable grass Festuca rubra was enhanced. Combined grazing by hares and cattle, resulted in homogenization of plant community composition on and off ant mounds, with high overall cover of F. rubra. We conclude that hares can respond to local ant–soil–vegetation interactions, because they are small, selective herbivores that make their foraging decisions on a local scale. This results in small-scale plant patches on mounds of yellow meadow ants. In the presence of cattle, which are less selective aboveground herbivores, local plant community patterns triggered by small-scale aboveground–belowground interactions can disappear. Therefore, cattle modify the consequences of aboveground–belowground interactions for small-scale plant community composition