Development of Dietary-Based Toxicity Reference Values to Assess the Risk of Chlorophacinone to Non-Target Raptorial Birds

Regulatory changes in the use of some second-generation anticoagulant rodenticides in parts of North America may result in expanded use of first-generation anticoagulant rodenticides (FGARs). Recent toxicological studies with captive raptors have demonstrated that these species are considerably more sensitive to the FGAR diphacinone than traditional avian wildlife test species (mallard, bobwhite). We have now examined the toxicity of the FGAR chlorophacinone (CPN) to American kestrels fed rat tissue mechanically amended with CPN, or rat tissue containing biologically-incorporated CPN, for 7 days. Nominal CPN concentrations in these diets were 0.15, 0.75, and 1.5 μg/g food wet weight, and actual CPN concentration in diets were analytically verified as being close to target values. Food intake was consistent among groups, body weight fluctuated by less than 6%, exposure and adverse effects were generally dose-dependent, and there were no dramatic differences in toxicity between mechanically-amended and biologically-incorporated CPN diets. Using benchmark dose statistical methods, toxicity reference values at which clotting times were prolonged in 50% of the kestrels was estimated to be about 80 μg CPN consumed/kg body weight-day for prothrombin time and 40 μg CPN/kg body weight-day for Russell’s viper venom time. Based upon carcass CPN residues reported in rodents from field baiting studies, empirical measures of food consumption in kestrels, and dietary-based toxicity reference values derived from the 7-day exposure scenario, some free-ranging raptors consuming CPN-exposed prey might exhibit coagulopathy and hemorrhage. These sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of exposed birds

Toxicity reference values for chlorophacinone and their application for assessing anticoagulant rodenticide risk to raptors

Despite widespread use and benefit, there are growing concerns regarding hazards of second-generation anticoagulant rodenticides to non-target wildlife which may result in expanded use of first-generation compounds, including chlorophacinone (CPN). The toxicity of CPN over a 7-day exposure period was investigated in American kestrels (Falco sparverius) fed either rat tissue mechanically- amended with CPN, tissue from rats fed Rozol bait (biologically-incorporated CPN), or control diets (tissue from untreated rats or commercial bird of prey diet) ad libitum. Nominal CPN concentrations in the formulated diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and measured concentrations averaged 94 % of target values. Kestrel food consumption was similar among groups and body weight varied by less than 6 %. Overt signs of intoxication, liver CPN residues, and changes in prothrombin time (PT), Russell’s viper venom time (RVVT) and hematocrit, were generally dose-dependent. Histological evidence of hemorrhage was present at all CPN dose levels, and most frequently observed in pectoral muscle and heart. There were no apparent differences in toxicity between mechanically-amended and biologically-incorporated CPN diet formulations. Dietary-based toxicity reference values at which clotting times were prolonged in 50 % of the kestrels were 79.2 µg CPN consumed/kg body weight-day for PT and 39.1 µg/kg body weight-day for RVVT. Based upon daily food consumption of kestrels and previously reported CPN concentrations found in small mammals following field baiting trials, these toxicity reference values might be exceeded by free-ranging raptors consuming such exposed prey. Tissue-based toxicity reference values for coagulopathy in 50 % of exposed birds were 0.107 µg CPN/g liver wet weight for PT and 0.076 µg/g liver for RVVT, and are below the range of residue levels reported in raptor mortality incidents attributed to CPN exposure. Sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of free-ranging raptors, and should be considered in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs

Left Motor delta Oscillations Reflect Asynchrony Detection in Multisensory Speech Perception

During multisensory speech perception, slow delta oscillations (∼1 - 3 Hz) in the listener's brain synchronize with the speech signal, likely engaging in speech signal decomposition. Notable fluctuations in the speech amplitude envelope, resounding speaker prosody, temporally align with articulatory and body gestures and both provide complementary sensations that temporally structure speech. Further, delta oscillations in the left motor cortex seem to align with speech and musical beats, suggesting their possible role in the temporal structuring of (quasi)-rhythmic stimulation. We extended the role of delta oscillations to audio-visual asynchrony detection as a test case of the temporal analysis of multisensory prosody fluctuations in speech. We recorded EEG responses in an audio-visual asynchrony detection task while participants watched videos of a speaker. We filtered the speech signal to remove verbal content and examined how visual and auditory prosodic features temporally (mis-)align. Results confirm (i) that participants accurately detected audio-visual asynchrony, and (ii) increased delta power in the left motor cortex in response to audio-visual asynchrony. The difference of delta power between asynchronous and synchronous conditions predicted behavioural performance, and (iii) decreased delta-beta coupling in the left motor cortex when listeners could not accurately map visual and auditory prosodies. Finally, both behavioural and neurophysiological evidence was altered when a speaker's face was degraded by a visual mask. Together, these findings suggest that motor delta oscillations support asynchrony detection of multisensory prosodic fluctuation in speech.SIGNIFICANCE STATEMENTSpeech perception is facilitated by regular prosodic fluctuations that temporally structure the auditory signal. Auditory speech processing involves the left motor cortex and associated delta oscillations. However, visual prosody (i.e., a speaker's body movements) complements auditory prosody, and it is unclear how the brain temporally analyses different prosodic features in multisensory speech perception. We combined an audio-visual asynchrony detection task with electroencephalographic recordings to investigate how delta oscillations support the temporal analysis of multisensory speech. Results confirmed that asynchrony detection of visual and auditory prosodies leads to increased delta power in left motor cortex and correlates with performance. We conclude that delta oscillations are invoked in an effort to resolve denoted temporal asynchrony in multisensory speech perception

Pathway Commons, a web resource for biological pathway data

Pathway Commons (http://www.pathwaycommons.org) is a collection of publicly available pathway data from multiple organisms. Pathway Commons provides a web-based interface that enables biologists to browse and search a comprehensive collection of pathways from multiple sources represented in a common language, a download site that provides integrated bulk sets of pathway information in standard or convenient formats and a web service that software developers can use to conveniently query and access all data. Database providers can share their pathway data via a common repository. Pathways include biochemical reactions, complex assembly, transport and catalysis events and physical interactions involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims to collect and integrate all public pathway data available in standard formats. Pathway Commons currently contains data from nine databases with over 1400 pathways and 687 000 interactions and will be continually expanded and updated

Altered reward system reactivity for personalized circumscribed interests in autism

Abstract Background Neurobiological research in autism spectrum disorders (ASD) has paid little attention on brain mechanisms that cause and maintain restricted and repetitive behaviors and interests (RRBIs). Evidence indicates an imbalance in the brain’s reward system responsiveness to social and non-social stimuli may contribute to both social deficits and RRBIs. Thus, this study’s central aim was to compare brain responsiveness to individual RRBI (i.e., circumscribed interests), with social rewards (i.e., social approval), in youth with ASD relative to typically developing controls (TDCs). Methods We conducted a 3T functional magnetic resonance imaging (fMRI) study to investigate the blood-oxygenation-level-dependent effect of personalized circumscribed interest rewards versus social rewards in 39 youth with ASD relative to 22 TDC. To probe the reward system, we employed short video clips as reinforcement in an instrumental incentive delay task. This optimization increased the task’s ecological validity compared to still pictures that are often used in this line of research. Results Compared to TDCs, youth with ASD had stronger reward system responses for CIs mostly within the non-social realm (e.g., video games) than social rewards (e.g., approval). Additionally, this imbalance within the caudate nucleus’ responsiveness was related to greater social impairment. Conclusions The current data support the idea of reward system dysfunction that may contribute to enhanced motivation for RRBIs in ASD, accompanied by diminished motivation for social engagement. If a dysregulated reward system indeed supports the emergence and maintenance of social and non-social symptoms of ASD, then strategically targeting the reward system in future treatment endeavors may allow for more efficacious treatment practices that help improve outcomes for individuals with ASD and their families

Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections

Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Toxicity reference values for chlorophacinone and their application for assessing anticoagulant rodenticide risk to raptors

Despite widespread use and benefit, there are growing concerns regarding hazards of second-generation anticoagulant rodenticides to non-target wildlife which may result in expanded use of first-generation compounds, including chlorophacinone (CPN). The toxicity of CPN over a 7-day exposure period was investigated in American kestrels (Falco sparverius) fed either rat tissue mechanically- amended with CPN, tissue from rats fed Rozol bait (biologically-incorporated CPN), or control diets (tissue from untreated rats or commercial bird of prey diet) ad libitum. Nominal CPN concentrations in the formulated diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and measured concentrations averaged 94 % of target values. Kestrel food consumption was similar among groups and body weight varied by less than 6 %. Overt signs of intoxication, liver CPN residues, and changes in prothrombin time (PT), Russell’s viper venom time (RVVT) and hematocrit, were generally dose-dependent. Histological evidence of hemorrhage was present at all CPN dose levels, and most frequently observed in pectoral muscle and heart. There were no apparent differences in toxicity between mechanically-amended and biologically-incorporated CPN diet formulations. Dietary-based toxicity reference values at which clotting times were prolonged in 50 % of the kestrels were 79.2 µg CPN consumed/kg body weight-day for PT and 39.1 µg/kg body weight-day for RVVT. Based upon daily food consumption of kestrels and previously reported CPN concentrations found in small mammals following field baiting trials, these toxicity reference values might be exceeded by free-ranging raptors consuming such exposed prey. Tissue-based toxicity reference values for coagulopathy in 50 % of exposed birds were 0.107 µg CPN/g liver wet weight for PT and 0.076 µg/g liver for RVVT, and are below the range of residue levels reported in raptor mortality incidents attributed to CPN exposure. Sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of free-ranging raptors, and should be considered in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

НАПРАВЛЕНИЯ СОВЕРШЕНСТВОВАНИЯ ОБРУДОВАНИЯ ДЛЯ ФЛОТАЦИОННОГО ОБОГАЩЕНИЯ ТОНКОДИСПЕРСНыХ МАТЕРИАЛОВ

Проблема и ее связь с научными и практическими задачами. В связи с тем, что в поступающем на обогатительные фабрики сырье содержится до 30% ма-териала крупностью менее 1 мм, роль процесса флотации существенно возрас-тает. Этому способствует и возможность создания достаточно простых замкну-тых водно-шламовых схем, включающих флотацию в качестве основного эле-мента очистки оборотных вод. Многими исследованиями, которые проводились ранее и продолжают выполняться и в настоящее время, установлены направле-ния совершенствования этого достаточно сложного физико-химического про-цесс

Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion