Formidable females redux: male social integration into female networks and the value of dynamic multilayer networks

The development of multilayer network techniques is a boon for researchers who wish to understand how different interaction layers might influence each other, and how these in turn might influence group dynamics. Here, we investigate how integration between male and female grooming and aggression interaction networks influences male power trajectories in vervet monkeys Chlorocebus pygerythrus. Our previous analyses of this phenomenon used a monolayer approach, and our aim here is to extend these analyses using a dynamic multilayer approach. To do so, we constructed a temporal series of male and female interaction layers. We then used a multivariate multilevel autoregression model to compare cross-lagged associations between a male’s centrality in the female grooming layer and changes in male Elo ratings. Our results confirmed our original findings: changes in male centrality within the female grooming network were weakly but positively tied to changes in their Elo ratings. However, the multilayer network approach offered additional insights into this social process, identifying how changes in a male’s centrality cascade through the other network layers. This dynamic view indicates that the changes in Elo ratings are likely to be short-lived, but that male centrality within the female network had a much stronger impact throughout the multilayer network as a whole, especially on reducing intermale aggression (i.e., aggression directed by males toward other males). We suggest that multilayer social network approaches can take advantage of increased amounts of social data that are more commonly collected these days, using a variety of methods. Such data are inherently multilevel and multilayered, and thus offer the ability to quantify more precisely the dynamics of animal social behaviors

Antihypertensive Drug Guanabenz Is Active In Vivo against both Yeast and Mammalian Prions

Background: Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans. [br/] Methodology/Principal Findings: Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of a2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrPSc clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on a2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals. [br/] Conclusion/Significance: GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases

Maternal social position and survival to weaning in arid‐country vervet monkeys

Objectives: We consider the relative contributions of maternal rank and sociability to the survival of infant vervet monkeys (Chlorocebus pygerythrus) to nutritional independence (~210 days) in a generally resource-poor environment. Methods: We analyzed survival data from 153 infants born to 60 mothers across three free-ranging troops and 10 yearly birth cohorts at a South African research site experiencing general but variable resource scarcity. Results: The population was characterized by a pre-weaning mortality of 30% (Range: 9%–85%), with a median age at death of 50 days. In addition to the consequences of resource availability, increased infant survival was independently and equivalently positively associated with higher maternal rank and a greater number of maternal spatial partners. Discussion: We use this outcome to suggest that apparent discrepancies across sites and species in the relative importance of different maternal attributes in determining reproductive outcomes may be resolved by considering more closely local sources of infant mortality

A Simple, Versatile and Sensitive Cell-Based Assay for Prions from Various Species

Detection and quantification of prion infectivity is a crucial step for various fundamental and applied aspects of prion research. Identification of cell lines highly sensitive to prion infection led to the development of cell-based titration procedures aiming at replacing animal bioassays, usually performed in mice or hamsters. However, most of these cell lines are only permissive to mouse-adapted prions strains and do not allow titration of prions from other species. In this study, we show that epithelial RK13, a cell line permissive to mouse and bank vole prion strains and to natural prion agents from sheep and cervids, enables a robust and sensitive detection of mouse and ovine-derived prions. Importantly, the cell culture work is strongly reduced as the RK13 cell assay procedure designed here does not require subcultivation of the inoculated cultures. We also show that prions effectively bind to culture plastic vessel and are quantitatively detected by the cell assay. The possibility to easily quantify a wider range of prions, including rodent experimental strains but also natural agents from sheep and cervids, should prompt the spread of cell assays for routine prion titration and lead to valuable information in fundamental and applied studies

Estimates of life history parameters in a high latitude, arid‐country vervet monkey population

We present data on life history parameters from a long‐term study of vervet monkeys in the Eastern Cape, South Africa. Estimates are presented of age at first conception for females and age at natal dispersal for males, along with the probability of survival to adulthood for infants born during the study, female reproductive life‐span, reproductive output (including lifetime reproductive success for a subset of females), and inter‐birth interval (IBI) duration. We also assess the effect of maternal age and infant survival on length of IBI. We then go on to compare life history parameters for our population with those from two East African populations in Kenya (Amboseli and Laikipia). We find there is broad consensus across the three populations, although mean infant survival was considerably lower for the two East African sites. Such comparisons must be made cautiously, however, as local ecology across the duration of the studies obviously has an impact on the estimates obtained. With this caveat in place, we consider that the concordance between values is sufficient to enable the values reported here to be used in comparative studies of primate life history, although data from habitats with higher rainfall and lower levels of seasonality are needed, and the results presented here should not be seen as canonical

Prion Protein Accumulation In Lipid Rafts of Mouse Aging Brain

The cellular form of the prion protein (PrP(C)) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C). In old mice, this change favors PrP(C) accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C) translocation into detergent-resistant membranes (DRMs), we looked at PrP(C) compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C) in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases

Identification of an Intracellular Site of Prion Conversion

Prion diseases are fatal, neurodegenerative disorders in humans and animals and are characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrPC), denoted PrPSc, which represents the major component of infectious scrapie prions. Characterization of the mechanism of conversion of PrPC into PrPSc and identification of the intracellular site where it occurs are among the most important questions in prion biology. Despite numerous efforts, both of these questions remain unsolved. We have quantitatively analyzed the distribution of PrPC and PrPSc and measured PrPSc levels in different infected neuronal cell lines in which protein trafficking has been selectively impaired. Our data exclude roles for both early and late endosomes and identify the endosomal recycling compartment as the likely site of prion conversion. These findings represent a fundamental step towards understanding the cellular mechanism of prion conversion and will allow the development of new therapeutic approaches for prion diseases

Prion protein interaction with soil humic substances: environmental implications

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders caused by prions. Animal TSE include scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids. Effective management of scrapie in many parts of the world, and of CWD in North American deer population is complicated by the persistence of prions in the environment. After shedding from diseased animals, prions persist in soil, withstanding biotic and abiotic degradation. As soil is a complex, multi-component system of both mineral and organic components, it is important to understand which soil compounds may interact with prions and thus contribute to disease transmission. Several studies have investigated the role of different soil minerals in prion adsorption and infectivity; we focused our attention on the interaction of soil organic components, the humic substances (HS), with recombinant prion protein (recPrP) material. We evaluated the kinetics of recPrP adsorption, providing a structural and biochemical characterization of chemical adducts using different experimental approaches. Here we show that HS act as potent anti-prion agents in prion infected neuronal cells and in the amyloid seeding assays: HS adsorb both recPrP and prions, thus sequestering them from the prion replication process. We interpreted our findings as highly relevant from an environmental point of view, as the adsorption of prions in HS may affect their availability and consequently hinder the environmental transmission of prion diseases in ruminants

Co-Orientation of Replication and Transcription Preserves Genome Integrity

In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication-disruption events, each of which is counter-selected independently because genome integrity is selected. To differentiate these possibilities and define the precise forces driving this aspect of genome organization, we generated new strains with inversions either over ∼1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying mathematical analysis to genomic microarray snapshots, we found that replication rates vary dramatically within the inverted genome. Replication is moderately impeded throughout the inverted region, which results in a small but significant competitive disadvantage in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA loci in rich medium. This obstruction results in disruption of DNA replication, activation of DNA damage responses, loss of genome integrity, and cell death. Our results strongly suggest that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization