UV-triggered Affinity Capture Identifies Interactions between the Plasmodium falciparum Multidrug Resistance Protein 1 (PfMDR1) and Antimalarial Agents in Live Parasitized Cells

A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites. We identified several proteins interacting with the capture compound and established a functional interaction between ACT-213615 and PfMDR1. We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615.     

Combination of yeast hydrolysates to improve CHO cell growth and IgG production

Many studies underlined the great benefits of hydrolysates used as additives in animal free media on cell culture performances. However, to precisely define hydrolysate supplementation strategies, a deeper understanding of their effect on cell growth and protein production is required. In the present study, the effect of addition of one yeast extract (YE) and two yeast peptones (named YP.A and YP.B) in a chemically defined medium was first assessed on cell culture performances. Interestingly, specific effects were found depending on the degree of degradation of yeast hydrolysates. The YE at 1 g L⁻¹ increased the maximal cell density by 70 %, while a mixture of YE (1 g L⁻¹) and YP.A (4 g L⁻¹) increased IgG production by 180 %. These conditions were then evaluated on the CHO cell kinetics all over cultures. Hydrolysates extended the cell growth phase in Erlenmeyer flask and increased the maximal growth rate in bioreactor up to 20 %. Cell growth stimulation induced by hydrolysates addition was linked with energetic metabolism improvement suggesting that they promote oxidative pathway. Furthermore, hydrolysates provided an additional source of substrate that supported cell growth despite glutamine limitation.     

Bifurcation analysis applied to a model of motion integration with a multistable stimulus

A computational study into the motion perception dynamics of a multistable psychophysics stimulus is presented. A diagonally drifting grating viewed through a square aperture is perceived as moving in the actual grating direction or in line with the aperture edges (horizontally or vertically). The different percepts are the product of interplay between ambiguous contour cues and specific terminator cues. We present a dynamical model of motion integration that performs direction selection for such a stimulus and link the different percepts to coexisting steady states of the underlying equations. We apply the powerful tools of bifurcation analysis and numerical continuation to study changes to the model’s solution structure under the variation of parameters. Indeed, we apply these tools in a systematic way, taking into account biological and mathematical constraints, in order to fix model parameters. A region of parameter space is identified for which the model reproduces the qualitative behaviour observed in experiments. The temporal dynamics of motion integration are studied within this region; specifically, the effect of varying the stimulus gain is studied, which allows for qualitative predictions to be made.     

Streamlined Development of Targeted Mass Spectrometry‐Based Method Combining Scout‐MRM and a Web‐Based Tool Indexed with Scout Peptides

MS‐based targeted proteomics is a relevant technology for sensitive and robust relative or absolute quantification of proteins biomarker candidates in complex human biofluids or tissue extracts. Performing a multiplex assay imposes time scheduling of peptide monitoring only around their expected retention time that needs to be defined with synthetic peptide. Time‐scheduled monitoring is clearly a constraint that precludes from straightforward assay transfer between biological matrices or distinct experimental setup. Any unexpected retention time (RT) shift challenges assay robustness and its implementation for large‐scale analysis. Recently, Scout‐multiple reaction monitoring that fully releases multiplexed targeted acquisition from RT scheduling by successively monitoring complex transition groups triggered with sentinel molecules called Scout has been introduced. It is herein documented how Peptide Selector database and tool streamlines the building of a multiplexed method thanks to RT indexation relative to Scout peptides. This case study deals with surrogate peptides of biomarker candidates related to drug‐induced liver and vascular injury, running such on‐line built method (eight Scouts triggering the monitoring of a total of 692 transitions) enables 100% recovery of a panel of 93 spiked‐in heavy labeled standards, despite significant RT shifts between serum, plasma, or urine. This result illustrates the simplicity of automatically building and deploying robust proteomics targeted assay.     

Halyomorpha halys (Stål 1855) en Île de France (Hemiptera : Pentatomidae : Pentatominae) : surveillons la punaise diabolique

Le Pentatomidae (Insecta : Hemiptera) d’origine asiatique Halyomorpha halys (Stal 1855) a été trouvée en Ile de France (Paris intra muros et Lardy, Essonne) à la fin de l’année 2013. Ces occurrences font suite à celle de l’été 2013 dans l’agglomération de Strasbourg, près de la frontière allemande. Il s’agit de la 5^e mention de cette espèce en Europe après la Suisse, l’Allemagne, et l’Italie. Il serait nécessaire de surveiller l’expansion de cette espèce polyphage et dommageable à des nombreuses cultures, dont l’expansion en Europe est très rapide, et qui peut être un agent allergénique.     

Adaptive properties of differential learning rates for positive and negative outcomes

The concept of the reward prediction error—the difference between reward obtained and reward predicted—continues to be a focal point for much theoretical and experimental work in psychology, cognitive science, and neuroscience. Models that rely on reward prediction errors typically assume a single learning rate for positive and negative prediction errors. However, behavioral data indicate that better-than-expected and worse-than-expected outcomes often do not have symmetric impacts on learning and decision-making. Furthermore, distinct circuits within cortico-striatal loops appear to support learning from positive and negative prediction errors, respectively. Such differential learning rates would be expected to lead to biased reward predictions and therefore suboptimal choice performance. Contrary to this intuition, we show that on static “bandit” choice tasks, differential learning rates can be adaptive. This occurs because asymmetric learning enables a better separation of learned reward probabilities. We show analytically how the optimal learning rate asymmetry depends on the reward distribution and implement a biologically plausible algorithm that adapts the balance of positive and negative learning rates from experience. These results suggest specific adaptive advantages for separate, differential learning rates in simple reinforcement learning settings and provide a novel, normative perspective on the interpretation of associated neural data.     

Correction: Simultaneous confidence regions for closed tests,including Holm‐, Hochberg‐, and Hommel‐related procedures

Algorithm 1 in Guilbaud (2012, p. 327) in Biometrical Journal (DOI: 10.1002/bimj.201100123 ) reproduced a recently detected index error in a theorem concerning a shortcut for rejection decisions for certain multiple‐testing procedures as it was stated in Bernhard et al. (2004, p. 8) in Statistical Papers (DOI: 10.1007/BF02778266 ). This short article provides: (i) the correction to be made to Algorithm 1 and (ii) a brief discussion of the consequences. Although the theoretical developments in Guilbaud (2012) are not affected, the numerical illustrations in Section 7 are affected. A corrected version of that section is given in the Supporting Information.     

Spatiotemporal Variation in Bonobo (Pan paniscus) Habitat Use in a Forest–Savanna Mosaic

International Journal of Primatology - Understanding the ecological and behavioral variation of primates is central to improving conservation strategies. Studies of chimpanzees (Pan troglodytes)...     

Alternative Confidence Regions for Bonferroni‐Based Closed‐Testing Procedures that are not Alpha‐Exhaustive

This article complements the results in Guilbaud (Biometrical Journal 2008; 50 :678–692). Simultaneous confidence regions were derived in that article that correspond to any given multiple testing procedure (MTP) in a fairly large class of consonant closed‐testing procedures based on marginal p‐values and weighted Bonferroni tests for intersection hypotheses. This class includes Holm's MTP, the fixed‐sequence MTP, gatekeeping MTPs, fallback MTPs, multi‐stage fallback MTPs, and recently proposed MTPs specified through a graphical representation and associated rejection algorithm. More general confidence regions are proposed in this article. These regions are such that for certain underlying MTPs which are not alpha‐exhaustive, they lead to confidence assertions that may be sharper than rejection assertions for some rejected null hypotheses H when not all Hs are rejected, which is not the case with the previously proposed regions. In fact, various alternative confidence regions may be available for such an underlying MTP. These results are shown through an extension of the previous direct arguments (without invoking the partitioning principle), and under the same general setup; so for instance, estimated quantities and marginal confidence regions are not restricted to be of any particular kinds/dimensions. The relation with corresponding confidence regions of Strassburger and Bretz (Statistics in Medicine 2008; 27 :4914–4927) is described. The results are illustrated with fallback and parallel‐gatekeeping MTPs.