Combined and single effects of pesticide carbaryl and toxic Microcystis aeruginosa on the life history of Daphnia pulicaria

The combined influence of a pesticide (carbaryl) and a cyanotoxin (microcystin LR) on the life history of Daphnia pulicaria was investigated. At the beginning of the experiments animals were pulse exposed to carbaryl for 24 h and microcystins were delivered bound in Microcystis’ cells at different, sub-lethal concentrations (chronic exposure). In order to determine the actual carbaryl concentrations in the water LC–MS/MS was used. For analyses of the cyanotoxin concentration in Daphnia’s body enzyme-linked immunosorbent assay (ELISA) was used. Individual daphnids were cultured in a flow-through system under constant light (16 h of light: 8 h of dark), temperature (20°C), and food conditions (Scenedesmus obliquus, 1 mg of C l−1). The results showed that in the treatments with carbaryl egg numbers per female did not differ significantly from controls, but the mortality of newborns increased significantly. Increasing microcystin concentrations significantly delayed maturation, reduced size at first reproduction, number of eggs, and newborns. The interaction between carbaryl and Microcystis was highly significant. Animals matured later and at a smaller size than in controls. The number of eggs per female was reduced as well. Moreover, combined stressors caused frequent premature delivery of offspring with body deformations such as dented carapax or an undeveloped heart. This effect is concluded to be synergistic and could not be predicted from the effects of the single stressors.

Bayesian Best-Arm Identification for Selecting Influenza Mitigation Strategies

Pandemic influenza has the epidemic potential to kill millions of people. While various preventive measures exist (i.a., vaccination and school closures), deciding on strategies that lead to their most effective and efficient use remains challenging. To this end, individual-based epidemiological models are essential to assist decision makers in determining the best strategy to curb epidemic spread. However, individual-based models are computationally intensive and it is therefore pivotal to identify the optimal strategy using a minimal amount of model evaluations. Additionally, as epidemiological modeling experiments need to be planned, a computational budget needs to be specified a priori. Consequently, we present a new sampling technique to optimize the evaluation of preventive strategies using fixed budget best-arm identification algorithms. We use epidemiological modeling theory to derive knowledge about the reward distribution which we exploit using Bayesian best-arm identification algorithms (i.e., Top-two Thompson sampling and BayesGap). We evaluate these algorithms in a realistic experimental setting and demonstrate that it is possible to identify the optimal strategy using only a limited number of model evaluations, i.e., 2-to-3 times faster compared to the uniform sampling method, the predominant technique used for epidemiological decision making in the literature. Finally, we contribute and evaluate a statistic for Top-two Thompson sampling to inform the decision makers about the confidence of an arm recommendation

Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the β2-adrenergic receptor

cAMP controls many cellular processes mainly through the activation of protein kinase A (PKA). However, more recently PKA-independent pathways have been established through the exchange protein directly activated by cAMP (Epac), a guanine nucleotide exchange factor for the small GTPases Rap1 and Rap2. In this report, we show that cAMP can induce integrin-mediated cell adhesion through Epac and Rap1. Indeed, when Ovcar3 cells were treated with cAMP, cells adhered more rapidly to fibronectin. This cAMP effect was insensitive to the PKA inhibitor H-89. A similar increase was observed when the cells were transfected with Epac. Both the cAMP effect and the Epac effect on cell adhesion were abolished by the expression of Rap1–GTPase-activating protein, indicating the involvement of Rap1 in the signaling pathway. Importantly, a recently characterized cAMP analogue, 8-(4-chloro-phenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate, which specifically activates Epac but not PKA, induced Rap-dependent cell adhesion. Finally, we demonstrate that external stimuli of cAMP signaling, i.e., isoproterenol, which activates the Gαs-coupled β2-adrenergic receptor can induce integrin-mediated cell adhesion through the Epac-Rap1 pathway. From these results we conclude that cAMP mediates receptor-induced integrin-mediated cell adhesion to fibronectin through the Epac-Rap1 signaling pathway

Evaluation and use of surveillance system data toward the identification of high-risk areas for potential cholera vaccination: a case study from Niger.

In 2008, Africa accounted for 94% of the cholera cases reported worldwide. Although the World Health Organization currently recommends the oral cholera vaccine in endemic areas for high-risk populations, its use in Sub-Saharan Africa has been limited. Here, we provide the principal results of an evaluation of the cholera surveillance system in the region of Maradi in Niger and an analysis of its data towards identifying high-risk areas for cholera

Measuring co-authorship and networking-adjusted scientific impact

Appraisal of the scientific impact of researchers, teams and institutions with productivity and citation metrics has major repercussions. Funding and promotion of individuals and survival of teams and institutions depend on publications and citations. In this competitive environment, the number of authors per paper is increasing and apparently some co-authors don't satisfy authorship criteria. Listing of individual contributions is still sporadic and also open to manipulation. Metrics are needed to measure the networking intensity for a single scientist or group of scientists accounting for patterns of co-authorship. Here, I define I1 for a single scientist as the number of authors who appear in at least I1 papers of the specific scientist. For a group of scientists or institution, In is defined as the number of authors who appear in at least In papers that bear the affiliation of the group or institution. I1 depends on the number of papers authored Np. The power exponent R of the relationship between I1 and Np categorizes scientists as solitary (R>2.5), nuclear (R=2.25-2.5), networked (R=2-2.25), extensively networked (R=1.75-2) or collaborators (R<1.75). R may be used to adjust for co-authorship networking the citation impact of a scientist. In similarly provides a simple measure of the effective networking size to adjust the citation impact of groups or institutions. Empirical data are provided for single scientists and institutions for the proposed metrics. Cautious adoption of adjustments for co-authorship and networking in scientific appraisals may offer incentives for more accountable co-authorship behaviour in published articles.Comment: 25 pages, 5 figure

An FHA domain–mediated protein interaction network of Rad53 reveals its role in polarized cell growth

The DNA damage checkpoint kinase Rad53 is important for the survival of budding yeast under genotoxic stresses. We performed a biochemical screen to identify proteins with specific affinity for the two Forkhead associated (FHA) domains of Rad53. The N-terminal FHA1 domain was found to coordinate a complex protein interaction network, which includes nuclear proteins involved in DNA damage checkpoints and transcriptional regulation. Unexpectedly, cytosolic proteins involved in cytokinesis, including septins, were also found as FHA1 binding proteins. Consistent with this interaction, a Rad53 mutant defective in its nuclear localization was found to localize to the bud neck. Abnormal morphology was observed in cells overexpressing the FHA1 domain and in rad53Δ cells under DNA replication stress. Further, septin Shs1 appears to have an important role in the response to DNA replication stress. Collectively, the results suggest a novel function of Rad53 in the regulation of polarized cell growth in response to DNA replication stress

Mobilisation of arsenic from bauxite residue (red mud) affected soils: effect of pH and redox conditions

The tailings dam breach at the Ajka alumina plant, western Hungary in 2010 introduced ~1 million m3 of red mud suspension into the surrounding area. Red mud (fine fraction bauxite residue) has a characteristically alkaline pH and contains several potentially toxic elements, including arsenic. Aerobic and anaerobic batch experiments were prepared using soils from near Ajka in order to investigate the effects of red mud addition on soil biogeochemistry and arsenic mobility in soil–water experiments representative of land affected by the red mud spill. XAS analysis showed that As was present in the red mud as As(V) in the form of arsenate. The remobilisation of red mud associated arsenate was highly pH dependent and the addition of phosphate to red mud suspensions greatly enhanced As release to solution. In aerobic batch experiments, where red mud was mixed with soils, As release to solution was highly dependent on pH. Carbonation of these alkaline solutions by dissolution of atmospheric CO2 reduced pH, which resulted in a decrease of aqueous As concentrations over time. However, this did not result in complete removal of aqueous As in any of the experiments. Carbonation did not occur in anaerobic experiments and pH remained high. Aqueous As concentrations initially increased in all the anaerobic red mud amended experiments, and then remained relatively constant as the systems became more reducing, both XANES and HPLC–ICP-MS showed that no As reduction processes occurred and that only As(V) species were present. These experiments show that there is the potential for increased As mobility in soil–water systems affected by red mud addition under both aerobic and anaerobic conditions