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    Assessment of stress responses in rhesus macaques (Macaca mulatta) to daily routine procedures in system neuroscience based on salivary cortisol concentrations 

    Pfefferle, Dana; Plümer, Sina; Burchardt, Leonore; Treue, Stefan; Gail, Alexander
    PLOS ONE 2018; 13(1): Art. e0190190
    Non-human primates participating in neurophysiological research are exposed to potentially stressful experimental procedures, such as dietary control protocols, surgical implants and their maintenance, or social separation during training and experimental session. Here, we investigated the effect of controlled access to fluid, surgical implants, implant-related cleaning of skin margins, and behavioral training sessions on salivary cortisol levels of adult male rhesus macaques participating in neurophysiological research. The animals were trained to chew flavored cotton swabs to non-invasively collect saliva samples. Our data show no differences in cortisol levels between animals with and without implants, but both, controlled access to fluid and cleaning of implants individually increased salivary cortisol concentrations, while both together did not further increase the concentration. Specifically, before cleaning, individuals with controlled access to fluid had 55% higher cortisol concentrations than individuals with free access to fluid. Under free access to fluid, cortisol concentrations were 27% higher after cleaning while no effect of cleaning was found for individuals under controlled fluid access. Training sessions under controlled access to fluid also did not affect salivary cortisol concentrations. The observed changes in cortisol concentrations represent mild stress responses, as they are only a fraction of the range of the regular circadian changes in cortisol levels in rhesus monkeys. They also indicate that combinations of procedures do not necessarily lead to cumulative stress responses. Our results indicate that salivary cortisol levels of rhesus monkeys respond to neurophysiological experimental procedures and, hence, may be used to assess further refinements of such experimental methods.
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    The Emotional Modulation of Facial Mimicry: A Kinematic Study 

    Tramacere, Antonella; Ferrari, Pier F.; Gentilucci, Maurizio; Giuffrida, Valeria; De Marco, Doriana
    Frontiers in Psychology 2017; 8: Art. 2339
    It is well-established that the observation of emotional facial expression induces facial mimicry responses in the observers. However, how the interaction between emotional and motor components of facial expressions can modulate the motor behavior of the perceiver is still unknown. We have developed a kinematic experiment to evaluate the effect of different oro-facial expressions on perceiver's face movements. Participants were asked to perform two movements, i.e., lip stretching and lip protrusion, in response to the observation of four meaningful (i.e., smile, angry-mouth, kiss, and spit) and two meaningless mouth gestures. All the stimuli were characterized by different motor patterns (mouth aperture or mouth closure). Response Times and kinematics parameters of the movements (amplitude, duration, and mean velocity) were recorded and analyzed. Results evidenced a dissociated effect on reaction times and movement kinematics. We found shorter reaction time when a mouth movement was preceded by the observation of a meaningful and motorically congruent oro-facial gesture, in line withfacial mimicryeffect. On the contrary, during execution, the perception of smile was associated with the facilitation, in terms of shorter duration and higher velocity of the incongruent movement, i.e., lip protrusion. The same effect resulted in response to kiss and spit that significantly facilitated the execution of lip stretching. We called this phenomenonfacial mimicry reversal effect, intended as the overturning of the effect normally observed during facial mimicry. In general, the findings show that both motor features and types of emotional oro-facial gestures (conveying positive or negative valence) affect the kinematics of subsequent mouth movements at different levels: while congruent motor features facilitate a general motor response, motor execution could be speeded by gestures that are motorically incongruent with the observed one. Moreover, valence effect depends on the specific movement required. Results are discussed in relation to the Basic Emotion Theory and embodied cognition framework.
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    Group size and visitor numbers predict faecal glucocorticoid concentrations in zoo meerkats. 

    Scott, Katy; Heistermann, Michael; Cant, Michael A.; Vitikainen, Emma I. K.
    Royal Society open science 2017; 4(4): Art. 161017
    Measures of physiological stress in zoo animals can give important insights into how they are affected by aspects of their captive environment. We analysed the factors influencing variation in glucocorticoid metabolites in faeces (fGCs) from zoo meerkats as a proxy for blood cortisol concentration, high levels of which are associated with a stress response. Levels of fGCs in captive meerkats declined with increasing group size. In the wild, very small groups of meerkats are at a higher risk of predation, while in larger groups, there is increased competition for resources. Indeed, group sizes in captivity resemble those seen in unstable coalitions in the wild, which may represent a stressful condition and predispose meerkats to chronic stress, even in the absence of natural predators. Individuals in large enclosures showed lower levels of stress, but meerkat density had no effect on the stress measures. In contrast with data from wild meerkats, neither sex, age nor dominance status predicted stress levels, which may reflect less food stress owing to more equal access to resources in captivity versus wild. The median number of visitors at the enclosure was positively correlated with fGC concentrations on the following day, with variation in the visitor numbers having the opposite effect. Our results are consistent with the hypothesis that there is an optimum group size which minimizes physiological stress in meerkats, and that zoo meerkats at most risk of physiological stress are those kept in small groups and small enclosures and are exposed to consistently high numbers of visitors.
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    Long-term consistency in spatial patterns of primate seed dispersal. 

    Heymann, Eckhard W.; Culot, Laurence; Knogge, Christoph; Noriega Piña, Tony Enrique; Tirado Herrera, Emérita R.; Klapproth, Matthias; Zinner, Dietmar
    Ecology and evolution 2017; 7(5) p.1435-1441
    Seed dispersal is a key ecological process in tropical forests, with effects on various levels ranging from plant reproductive success to the carbon storage potential of tropical rainforests. On a local and landscape scale, spatial patterns of seed dispersal create the template for the recruitment process and thus influence the population dynamics of plant species. The strength of this influence will depend on the long-term consistency of spatial patterns of seed dispersal. We examined the long-term consistency of spatial patterns of seed dispersal with spatially explicit data on seed dispersal by two neotropical primate species, Leontocebus nigrifrons and Saguinus mystax (Callitrichidae), collected during four independent studies between 1994 and 2013. Using distributions of dispersal probability over distances independent of plant species, cumulative dispersal distances, and kernel density estimates, we show that spatial patterns of seed dispersal are highly consistent over time. For a specific plant species, the legume Parkia panurensis, the convergence of cumulative distributions at a distance of 300 m, and the high probability of dispersal within 100 m from source trees coincide with the dimension of the spatial-genetic structure on the embryo/juvenile (300 m) and adult stage (100 m), respectively, of this plant species. Our results are the first demonstration of long-term consistency of spatial patterns of seed dispersal created by tropical frugivores. Such consistency may translate into idiosyncratic patterns of regeneration.
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    A combination of NMDA and AMPA receptor antagonists retards granule cell dispersion and epileptogenesis in a model of acquired epilepsy. 

    Schidlitzki, Alina; Twele, Friederike; Klee, Rebecca; Waltl, Inken; Römermann, Kerstin; Bröer, Sonja; Meller, Sebastian; Gerhauser, Ingo; Rankovic, Vladan; Li, Dandan; et al.
    Brandt, ClaudiaBankstahl, MarionTöllner, KathrinLöscher, Wolfgang
    Scientific reports 2017-09-22; 7(1): Art. 12191
    Epilepsy may arise following acute brain insults, but no treatments exist that prevent epilepsy in patients at risk. Here we examined whether a combination of two glutamate receptor antagonists, NBQX and ifenprodil, acting at different receptor subtypes, exerts antiepileptogenic effects in the intrahippocampal kainate mouse model of epilepsy. These drugs were administered over 5 days following kainate. Spontaneous seizures were recorded by video/EEG at different intervals up to 3 months. Initial trials showed that drug treatment during the latent period led to higher mortality than treatment after onset of epilepsy, and further, that combined therapy with both drugs caused higher mortality at doses that appear safe when used singly. We therefore refined the combined-drug protocol, using lower doses. Two weeks after kainate, significantly less mice of the NBQX/ifenprodil group exhibited electroclinical seizures compared to vehicle controls, but this effect was lost at subsequent weeks. The disease modifying effect of the treatment was associated with a transient prevention of granule cell dispersion and less neuronal degeneration in the dentate hilus. These data substantiate the involvement of altered glutamatergic transmission in the early phase of epileptogenesis. Longer treatment with NBQX and ifenprodil may shed further light on the apparent temporal relationship between dentate gyrus reorganization and development of spontaneous seizures.
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    Haemophilus ducreyi DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea. 

    Houinei, Wendy; Godornes, Charmie; Kapa, August; Knauf, Sascha; Mooring, Eric Q.; González-Beiras, Camila; Watup, Ronald; Paru, Raymond; Advent, Paul; Bieb, Sivauk; et al.
    Sanz, SergiBassat, QuiqueSpinola, Stanley M.Lukehart, Sheila A.Mitjà, Oriol
    PLoS neglected tropical diseases 2017-05; 11(5): Art. e0004958
    BACKGROUND: Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major causes of leg ulcers in children in Africa and the Pacific Region. We investigated the presence of DNA (PCR positivity) from these bacteria on asymptomatic people, flies, and household linens in an endemic setting. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional study in rural villages of Lihir Island, Papua New Guinea during a yaws elimination campaign. Participants were asymptomatic subjects recruited from households with cases of leg ulcers, and from households without cases of leg ulcers. We rubbed swabs on the intact skin of the leg of asymptomatic individuals, and collected flies and swabs of environmental surfaces. All specimens were tested by PCR for H. ducreyi and T. p. pertenue DNA. Of 78 asymptomatic participants that had an adequate specimen for DNA detection, H. ducreyi-PCR positivity was identified in 16 (21%) and T. p. pertenue-PCR positivity in 1 (1%). In subgroup analyses, H. ducreyi-PCR positivity did not differ in participants exposed or not exposed to a case of H. ducreyi ulcer in the household (24% vs 18%; p = 0.76). Of 17 cultures obtained from asymptomatic participants, 2 (12%) yielded a definitive diagnosis of H. ducreyi, proving skin colonization. Of 10 flies tested, 9 (90%) had H. ducreyi DNA and 5 (50%) had T. p. pertenue DNA. Of 6 bed sheets sampled, 2 (33%) had H. ducreyi DNA and 1 (17%) had T. p. pertenue DNA. CONCLUSIONS/SIGNIFICANCE: This is the first time that H. ducreyi DNA and colonization has been demonstrated on the skin of asymptomatic children and that H. ducreyi DNA and T. p. pertenue DNA has been identified in flies and on fomites. The ubiquity of H. ducreyi in the environment is a contributing factor to the spread of the organism.
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    Disease reservoirs: from conceptual frameworks to applicable criteria. 

    Hallmaier-Wacker, Luisa K; Munster, Vincent J; Knauf, Sascha
    Emerging microbes & infections 2017-09-06; 6(9): Art. e79
    Central to the One Health approach and any disease eradication program is the question of whether a pathogen has a non-human reservoir. Despite well-established conceptual frameworks that define a reservoir of infection, empirical characterization of reservoirs often remains controversial, challenging and sometimes misleading. What is essentially missing are applicable requirements that standardize the use of the term 'reservoir of infection' across multiple disciplines. We propose an empirical framework, considering maintenance and feasible transmission of a pathogen, to standardize the acceptance of a disease reservoir across multiple disciplines. We demonstrate the intended use of these requirements by applying them to different diseases that are known to infect both humans and animals.
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    Evidence for Human Streptococcus pneumoniae in wild and captive chimpanzees: A potential threat to wild populations. 

    Köndgen, Sophie; Calvignac-Spencer, Sebastien; Grützmacher, Kim; Keil, Verena; Mätz-Rensing, Kerstin; Nowak, Kathrin; Metzger, Sonja; Kiyang, John; Becker, Antina Lübke; Deschner, Tobias; et al.
    Wittig, Roman MLankester, FelixLeendertz, Fabian H
    Scientific reports 2017-11-06; 7(1): Art. 14581
    Habituation of wild great apes for tourism and research has had a significant positive effect on the conservation of these species. However, risks associated with such activities have been identified, specifically the transmission of human respiratory viruses to wild great apes, causing high morbidity and, occasionally, mortality. Here, we investigate the source of bacterial-viral co-infections in wild and captive chimpanzee communities in the course of several respiratory disease outbreaks. Molecular analyses showed that human respiratory syncytial viruses (HRSV) and human metapneumoviruses (HMPV) were involved in the etiology of the disease. In addition our analysis provide evidence for coinfection with Streptococcus (S.) pneumoniae. Characterisation of isolates from wild chimpanzees point towards a human origin of these bacteria. Transmission of these bacteria is of concern because - in contrast to HRSV and HMPV - S. pneumoniae can become part of the nasopharyngeal flora, contributing to the severity of respiratory disease progression. Furthermore these bacteria have the potential to spread to other individuals in the community and ultimately into the population. Targeted vaccination programs could be used to vaccinate habituated great apes but also human populations around great ape habitats, bringing health benefits to both humans and wild great apes.
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    Evolution of facial color pattern complexity in lemurs. 

    Rakotonirina, Hanitriniaina; Kappeler, Peter M.; Fichtel, Claudia
    Scientific reports 2017-11-09; 7(1): Art. 15181
    Interspecific variation in facial color patterns across New and Old World primates has been linked to species recognition and group size. Because group size has opposite effects on interspecific variation in facial color patterns in these two radiations, a study of the third large primate radiation may shed light on convergences and divergences in this context. We therefore compiled published social and ecological data and analyzed facial photographs of 65 lemur species to categorize variation in hair length, hair and skin coloration as well as color brightness. Phylogenetically controlled analyses revealed that group size and the number of sympatric species did not influence the evolution of facial color complexity in lemurs. Climatic factors, however, influenced facial color complexity, pigmentation and hair length in a few facial regions. Hair length in two facial regions was also correlated with group size and may facilitate individual recognition. Since phylogenetic signals were moderate to high for most models, genetic drift may have also played a role in the evolution of facial color patterns of lemurs. In conclusion, social factors seem to have played only a subordinate role in the evolution of facial color complexity in lemurs, and, more generally, group size appears to have no systematic functional effect on facial color complexity across all primates.
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    Low Levels of Fruit Nitrogen as Drivers for the Evolution of Madagascar's Primate Communities. 

    Donati, Giuseppe; Santini, Luca; Eppley, Timothy M.; Arrigo-Nelson, Summer J.; Balestri, Michela; Boinski, Sue; Bollen, An; Bridgeman, LeAndra L.; Campera, Marco; Carrai, Valentina; et al.
    Chalise, Mukesh K.Derby Lewis, AbigailHohmann, GottfriedKinnaird, Margaret F.Koenig, AndreasKowalewski, MartinLahann, PetraMcLennan, Matthew R.Nekaris, Anna K. I.Nijman, VincentNorscia, IvanOstner, JuliaPolowinsky, Sandra Y.Schülke, OliverSchwitzer, ChristophStevenson, Pablo R.Talebi, Mauricio G.Tan, ChiaTomaschewski, IreneVogel, Erin R.Wright, Patricia C.Ganzhorn, Jörg U.
    Scientific reports 2017-10-31; 7(1): Art. 14406
    The uneven representation of frugivorous mammals and birds across tropical regions - high in the New World, low in Madagascar and intermediate in Africa and Asia - represents a long-standing enigma in ecology. Several hypotheses have been proposed to explain these differences but the ultimate drivers remain unclear. Here, we tested the hypothesis that fruits in Madagascar contain insufficient nitrogen to meet primate metabolic requirements, thus constraining the evolution of frugivory. We performed a global analysis of nitrogen in fruits consumed by primates, as collated from 79 studies. Our results showed that average frugivory among lemur communities was lower compared to New World and Asian-African primate communities. Fruits in Madagascar contain lower average nitrogen than those in the New World and Old World. Nitrogen content in the overall diets of primate species did not differ significantly between major taxonomic radiations. There is no relationship between fruit protein and the degree of frugivory among primates either globally or within regions, with the exception of Madagascar. This suggests that low protein availability in fruits influences current lemur communities to select for protein from other sources, whereas in the New World and Old World other factors are more significant in shaping primate communities.
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    Sexual dimorphism of AMBRA1-related autistic features in human and mouse. 

    Mitjans, M.; Begemann, M.; Ju, A.; Dere, E.; Wüstefeld, L.; Hofer, S.; Hassouna, I.; Balkenhol, J.; Oliveira, B.; van der Auwera, S.; et al.
    Tammer, R.Hammerschmidt, K.Völzke, H.Homuth, G.Cecconi, F.Chowdhury, K.Grabe, H.Frahm, J.Boretius, S.Dandekar, T.Ehrenreich, H.
    Translational psychiatry 2017-10-10; 7(10): Art. e1247
    Ambra1 is linked to autophagy and neurodevelopment. Heterozygous Ambra1 deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of AMBRA1 for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal AMBRA1 genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower AMBRA1 mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by in silico analysis. Searching for further autism-relevant characteristics in Ambra1(+/-) mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an in vivo readout of neuronal excitation-inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of AMBRA1/Ambra1 partial loss-of-function genotypes for female autistic traits. Moreover, they suggest Ambra1 heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism.
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    Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy 

    Jo, Peter; Azizian, Azadeh; Salendo, Junius; Kramer, Frank; Bernhardt, Markus; Wolff, Hendrik; Gruber, Jens; Grade, Marian; Beißbarth, Tim; Ghadimi, B.; et al.
    Gaedcke, Jochen
    International Journal of Molecular Sciences 2017; 18(6): Art. 1140
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    Self-cytoplasmic DNA upregulates the mutator enzyme APOBEC3A leading to chromosomal DNA damage 

    Suspène, Rodolphe; Mussil, Bianka; Laude, Hélène; Caval, Vincent; Berry, Noémie; Bouzidi, Mohamed S.; Thiers, Valérie; Wain-Hobson, Simon; Vartanian, Jean-Pierre
    Nucleic Acids Research 2017; 45(6) p.3231-3241
    Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A. By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal. The price to pay is chromosomal DNA damage in the form of CG→TA mutations and double stranded DNA breaks which, in the context of chronic inflammation, could drive cells down the path toward cancer.
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    Differential contribution of immune effector mechanisms to cortical demyelination in multiple sclerosis 

    Lagumersindez-Denis, Nielsen; Wrzos, Claudia; Mack, Matthias; Winkler, Anne; van der Meer, Franziska; Reinert, Marie C.; Hollasch, Heiko; Flach, Anne; Brühl, Hilke; Cullen, Eilish; et al.
    Schlumbohm, ChristinaFuchs, EberhardLinington, ChristopherBarrantes-Freer, AlonsoMetz, ImkeWegner, ChristianeLiebetanz, DavidPrinz, MarcoBrück, WolfgangStadelmann, ChristineNessler, Stefan
    Acta Neuropathologica 2017; 134(1) p.15-34
    Cortical demyelination is a widely recognized hallmark of multiple sclerosis (MS) and correlate of disease progression and cognitive decline. The pathomechanisms initiating and driving gray matter damage are only incompletely understood. Here, we determined the infiltrating leukocyte subpopulations in 26 cortical demyelinated lesions of biopsied MS patients and assessed their contribution to cortical lesion formation in a newly developed mouse model. We find that conformation-specific anti-myelin antibodies contribute to cortical demyelination even in the absence of the classical complement pathway. T cells and natural killer cells are relevant for intracortical type 2 but dispensable for subpial type 3 lesions, whereas CCR2+ monocytes are required for both. Depleting CCR2+ monocytes in marmoset monkeys with experimental autoimmune encephalomyelitis using a novel humanized CCR2 targeting antibody translates into significantly less cortical demyelination and disease severity. We conclude that biologics depleting CCR2+ monocytes might be attractive candidates for preventing cortical lesion formation and ameliorating disease progression in MS.
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    Recent expansion and adaptive evolution of the carcinoembryonic antigen family in bats of the Yangochiroptera subgroup 

    Kammerer, Robert; Mansfeld, Martin; Hänske, Jana; Mißbach, Sophie; He, Xiaocui; Köllner, Bernd; Mouchantat, Susan; Zimmermann, Wolfgang
    BMC Genomics 2017; 18(1)
    BACKGROUND: Expansions of gene families are predictive for ongoing genetic adaptation to environmental cues. We describe such an expansion of the carcinoembryonic antigen (CEA) gene family in certain bat families. Members of the CEA family in humans and mice are exploited as cellular receptors by a number of pathogens, possibly due to their function in immunity and reproduction. The CEA family is composed of CEA-related cell adhesion molecules (CEACAMs) and secreted pregnancy-specific glycoproteins (PSGs). PSGs are almost exclusively expressed by trophoblast cells at the maternal-fetal interface. The reason why PSGs exist only in a minority of mammals is still unknown. RESULTS: Analysis of the CEA gene family in bats revealed that in certain bat families, belonging to the subgroup Yangochiroptera but not the Yinpterochiroptera subgroup an expansion of the CEA gene family took place, resulting in approximately one hundred CEA family genes in some species of the Vespertilionidae. The majority of these genes encode secreted PSG-like proteins (further referred to as PSG). Remarkably, we found strong evidence that the ligand-binding domain (IgV-like domain) of PSG is under diversifying positive selection indicating that bat PSGs may interact with structurally highly variable ligands. Such ligands might represent bacterial or viral pathogen adhesins. We have identified two distinct clusters of PSGs in three Myotis species. The two PSG cluster differ in the amino acids under positive selection. One cluster was only expanded in members of the Vespertilionidae while the other was found to be expanded in addition in members of the Miniopteridae and Mormoopidae. Thus one round of PSG expansion may have occurred in an ancestry of all three families and a second only in Vespertilionidae. Although maternal ligands of PSGs may exist selective challenges by two distinct pathogens seem to be likely responsible for the expansion of PSGs in Vespertilionidae. CONCLUSIONS: The rapid expansion of PSGs in certain bat species together with selection for diversification suggest that bat PSGs could be part of a pathogen defense system by serving as decoy receptors and/or regulators of feto-maternal interactions.
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    Hair cortisol concentrations correlate negatively with survival in a wild primate population 

    Rakotoniaina, Josué H.; Kappeler, Peter M.; Kaesler, Eva; Hämäläinen, Anni M.; Kirschbaum, Clemens; Kraus, Cornelia
    BMC Ecology 2017; 17(1)
    BACKGROUND: Glucocorticoid hormones are known to play a key role in mediating a cascade of physiological responses to social and ecological stressors and can therefore influence animals' behaviour and ultimately fitness. Yet, how glucocorticoid levels are associated with reproductive success or survival in a natural setting has received little empirical attention so far. Here, we examined links between survival and levels of glucocorticoid in a small, short-lived primate, the grey mouse lemur (Microcebus murinus), using for the first time an indicator of long-term stress load (hair cortisol concentration). Using a capture-mark-recapture modelling approach, we assessed the effect of stress on survival in a broad context (semi-annual rates), but also under a specific period of high energetic demands during the reproductive season. We further assessed the power of other commonly used health indicators (body condition and parasitism) in predicting survival outcomes relative to the effect of long-term stress. RESULTS: We found that high levels of hair cortisol were associated with reduced survival probabilities both at the semi-annual scale and over the reproductive season. Additionally, very good body condition (measured as scaled mass index) was related to increased survival at the semi-annual scale, but not during the breeding season. In contrast, variation in parasitism failed to predict survival. CONCLUSION: Altogether, our results indicate that long-term increased glucocorticoid levels can be related to survival and hence population dynamics, and suggest differential strength of selection acting on glucocorticoids, body condition, and parasite infection.
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    What makes a reach movement effortful? Physical effort discounting supports common minimization principles in decision making and motor control. 

    Morel, Pierre; Ulbrich, Philipp; Gail, Alexander
    PLoS biology 2017-06; 15(6): Art. e2001323
    When deciding between alternative options, a rational agent chooses on the basis of the desirability of each outcome, including associated costs. As different options typically result in different actions, the effort associated with each action is an essential cost parameter. How do humans discount physical effort when deciding between movements? We used an action-selection task to characterize how subjective effort depends on the parameters of arm transport movements and controlled for potential confounding factors such as delay discounting and performance. First, by repeatedly asking subjects to choose between 2 arm movements of different amplitudes or durations, performed against different levels of force, we identified parameter combinations that subjects experienced as identical in effort (isoeffort curves). Movements with a long duration were judged more effortful than short-duration movements against the same force, while movement amplitudes did not influence effort. Biomechanics of the movements also affected effort, as movements towards the body midline were preferred to movements away from it. Second, by introducing movement repetitions, we further determined that the cost function for choosing between effortful movements had a quadratic relationship with force, while choices were made on the basis of the logarithm of these costs. Our results show that effort-based action selection during reaching cannot easily be explained by metabolic costs. Instead, force-loaded reaches, a widely occurring natural behavior, imposed an effort cost for decision making similar to cost functions in motor control. Our results thereby support the idea that motor control and economic choice are governed by partly overlapping optimization principles.
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    Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2. 

    Reinke, Lennart Michel; Spiegel, Martin; Plegge, Teresa; Hartleib, Anika; Nehlmeier, Inga; Gierer, Stefanie; Hoffmann, Markus; Hofmann-Winkler, Heike; Winkler, Michael; Pöhlmann, Stefan
    PloS one 2017; 12(6): Art. e0179177
    The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) mediates viral entry into target cells. Cleavage and activation of SARS S by a host cell protease is essential for infectious viral entry and the responsible enzymes are potential targets for antiviral intervention. The type II transmembrane serine protease TMPRSS2 cleaves and activates SARS S in cell culture and potentially also in the infected host. Here, we investigated which determinants in SARS S control cleavage and activation by TMPRSS2. We found that SARS S residue R667, a previously identified trypsin cleavage site, is also required for S protein cleavage by TMPRSS2. The cleavage fragments produced by trypsin and TMPRSS2 differed in their decoration with N-glycans, suggesting that these proteases cleave different SARS S glycoforms. Although R667 was required for SARS S cleavage by TMPRSS2, this residue was dispensable for TMPRSS2-mediated S protein activation. Conversely, residue R797, previously reported to be required for SARS S activation by trypsin, was dispensable for S protein cleavage but required for S protein activation by TMPRSS2. Collectively, these results show that different residues in SARS S control cleavage and activation by TMPRSS2, suggesting that these processes are more complex than initially appreciated.
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    Meerkat close calling patterns are linked to sex, social category, season and wind, but not fecal glucocorticoid metabolite concentrations 

    Mausbach, Jelena; Braga Goncalves, Ines; Heistermann, Michael; Ganswindt, André; Manser, Marta B.
    PLOS ONE 2017; 12(5): Art. e0175371
    It is well established that animal vocalizations can encode information regarding a sender’s identity, sex, age, body size, social rank and group membership. However, the association between physiological parameters, particularly stress hormone levels, and vocal behavior is still not well understood. The cooperatively breeding African meerkats (Suricata suricatta) live in family groups with despotic social hierarchies. During foraging, individuals emit close calls that help maintain group cohesion. These contact calls are acoustically distinctive and variable in rate across individuals, yet, information on which factors influence close calling behavior is missing. The aim of this study was to identify proximate factors that influence variation in call rate and acoustic structure of meerkat close calls. Specifically, we investigated whether close calling behavior is associated with sex, age and rank, or stress hormone output (i.e., measured as fecal glucocorticoid metabolite (fGCM) concentrations) as individual traits of the caller, as well as with environmental conditions (weather) and reproductive seasonality. To disentangle the effects of these factors on vocal behavior, we analyzed sound recordings and assessed fGCM concentrations in 64 wild but habituated meerkats from 9 groups during the reproductive and non-reproductive seasons. Dominant females and one-year old males called at significantly higher rates compared to other social categories during the reproductive season. Additionally, dominant females produced close calls with the lowest mean fundamental frequencies (F0) and the longest mean pulse durations. Windy conditions were associated with significantly higher call rates during the non-reproductive season. Fecal GCM concentrations were unrelated to close calling behavior. Our findings suggest that meerkat close calling behavior conveys information regarding the sex and social category of the caller, but shows no association with fGCM concentrations. The change in call rate in response to variation in the social and ecological environments individuals experience indicates some degree of flexibility in vocal production.
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    Non-human primate orthologues of TMPRSS2 cleave and activate the influenza virus hemagglutinin 

    Zmora, Pawel; Molau-Blazejewska, Paulina; Bertram, Stephanie; Walendy-Gnirß, Kerstin; Nehlmeier, Inga; Hartleib, Anika; Moldenhauer, Anna-Sophie; Konzok, Sebastian; Dehmel, Susann; Sewald, Katherina; et al.
    Brinkmann, ConstantinCurths, ChristophKnauf, SaschaGruber, JensMätz-Rensing, KerstinDahlmann, FranziskaBraun, ArminPöhlmann, Stefan
    PLOS ONE 2017; 12(5): Art. e0176597
    The cellular serine protease TMPRSS2, a member of the type II transmembrane serine protease (TTSP) family, cleaves and activates the hemagglutinin of influenza A viruses (FLUAV) in cell culture and is essential for spread of diverse FLUAV in mice. Non-human primates (NHP), in particular rhesus and cynomolgus macaques, serve as animal models for influenza and experimental FLUAV infection of common marmosets has recently also been reported. However, it is currently unknown whether the NHP orthologues of human TMPRSS2 cleave and activate FLUAV hemagglutinin and contribute to viral spread in respiratory tissue. Here, we cloned and functionally analyzed the macaque and marmoset orthologues of human TMPRSS2. In addition, we analyzed the macaque orthologues of human TMPRSS4 and HAT, which also belong to the TTSP family. We found that all NHP orthologues of human TMPRSS2, TMPRSS4 and HAT cleave and activate HA upon directed expression and provide evidence that endogenous TMPRSS2 is expressed in the respiratory epithelium of rhesus macaques. Finally, we demonstrate that a serine protease inhibitor active against TMPRSS2 suppresses FLUAV spread in precision-cut lung slices of human, macaque and marmoset origin. These results indicate that FLUAV depends on serine protease activity for spread in diverse NHP and in humans. Moreover, our findings suggest that macaques and marmosets may serve as models to study FLUAV activation by TMPRSS2 in human patients.
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