Items 1-20 of 293

    • Journal Article

      Near physiological spectral selectivity of cochlear optogenetics 

      Dieter, Alexander; Duque-Afonso, Carlos J.; Rankovic, Vladan; Jeschke, Marcus; Moser, Tobias
      Nature Communications 2019; 10(1): Art. 1962
      Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) and partially restore hearing to half a million CI users. However, wide current spread from intracochlear electrodes limits spatial selectivity (i.e. spectral resolution) of electrical CIs. Optogenetic stimulation might become an alternative, since light can be confined in space, promising artificial sound encoding with increased spectral selectivity. Here we compare spectral selectivity of optogenetic, electric, and acoustic stimulation by multi-channel recordings in the inferior colliculus (IC) of gerbils. When projecting light onto tonotopically distinct SGNs, we observe corresponding tonotopically ordered IC activity. An activity-based comparison reveals that spectral selectivity of optogenetic stimulation is indistinguishable from acoustic stimulation for modest intensities. Moreover, optogenetic stimulation outperforms bipolar electric stimulation at medium and high intensities and monopolar electric stimulation at all intensities. In conclusion, we demonstrate better spectral selectivity of optogenetic over electric SGN stimulation, suggesting the potential for improved hearing restoration by optical CIs.
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    • Journal Article

      Acoustic variation of spider monkey (Ateles geoffroyi) contact calls is related to caller isolation and affects listeners’ responses 

      Ordóñez-Gómez, José D.; Santillan-Doherty, Ana M.; Hammerschmidt, Kurt
      PLOS ONE 2019; 14(4): Art. e0213914
      Group living animals produce vocalizations denominated "contact calls" to maintain contact with out-of-sight group members. These calls have been shown to vary with caller identity and distance to potential listeners. However, it is not clear whether the acoustic variation of contact calls is related to caller social isolation (e.g., inside or outside a subgroup) and listeners' responses that can be helpful to maintain contact. Here, we addressed these questions in spider monkeys (Ateles geoffroyi), a Neotropical primate that exchanges contact calls denominated "whinnies", which show graded variation related to caller immediate behavior and distance between callers. Using 566 whinnies produced by 35 free-ranging adult spider monkeys recorded at ≤ 20 m from microphones, we first analyzed whether the acoustic variation of spontaneous whinnies (i.e., whinnies that are not responses to previous whinnies) is related to caller social isolation or whether acoustic variation is related to the likelihood of eliciting a response whinny from another individual. Secondly, we assessed whether listeners' responses (i.e., time to respond vocally, acoustic characteristics of response whinnies, orienting behaviors) were related to the acoustic variation of previous whinnies. Our study revealed that callers that were outside a subgroup produced whinnies with a lower fundamental frequency (F0), which travels longer distances, and increases the likelihood of producing a response whinny. Moreover, listeners (i.e., responders) responded faster to lower F0 whinnies. However, the acoustic variation (i.e., F0 variation) in response whinnies was better explained by the separation distance between callers, than by the acoustic variation of the previous whinny. Overall, our results suggest that whinny variation facilitates vocal contact to callers that are outside a subgroup, and that context and whinny variation affect listeners' responses.
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    • Journal Article

      Inhibitors of signal peptide peptidase and subtilisin/kexin-isozyme 1 inhibit Ebola virus glycoprotein-driven cell entry by interfering with activity and cellular localization of endosomal cathepsins 

      Plegge, Teresa; Spiegel, Martin; Krüger, Nadine; Nehlmeier, Inga; Winkler, Michael; González Hernández, Mariana; Pöhlmann, Stefan
      PLOS ONE 2019; 14(4): Art. e0214968
      Emerging viruses such as severe fever and thrombocytopenia syndrome virus (SFTSV) and Ebola virus (EBOV) are responsible for significant morbidity and mortality. Host cell proteases that process the glycoproteins of these viruses are potential targets for antiviral intervention. The aspartyl protease signal peptide peptidase (SPP) has recently been shown to be required for processing of the glycoprotein precursor, Gn/Gc, of Bunyamwera virus and for viral infectivity. Here, we investigated whether SPP is also required for infectivity of particles bearing SFTSV-Gn/Gc. Entry driven by the EBOV glycoprotein (GP) and the Lassa virus glycoprotein (LASV-GPC) depends on the cysteine proteases cathepsin B and L (CatB/CatL) and the serine protease subtilisin/kexin-isozyme 1 (SKI-1), respectively, and was examined in parallel for control purposes. We found that inhibition of SPP and SKI-1 did not interfere with SFTSV Gn + Gc-driven entry but, unexpectedly, blocked entry mediated by EBOV-GP. The inhibition occurred at the stage of proteolytic activation and the SPP inhibitor was found to block CatL/CatB activity. In contrast, the SKI-1 inhibitor did not interfere with CatB/CatL activity but disrupted CatB localization in endo/lysosomes, the site of EBOV-GP processing. These results underline the potential of protease inhibitors for antiviral therapy but also show that previously characterized compounds might exert broader specificity than initially appreciated and might block viral entry via diverse mechanisms.
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    • Journal Article

      Neural coding of intended and executed grasp force in macaque areas AIP, F5, and M1 

      Intveld, Rijk W.; Dann, Benjamin; Michaels, Jonathan A.; Scherberger, Hansjörg
      Scientific Reports 2018; 8(1): Art. 17985
      Considerable progress has been made over the last decades in characterizing the neural coding of hand shape, but grasp force has been largely ignored. We trained two macaque monkeys (Macaca mulatta) on a delayed grasping task where grip type and grip force were instructed. Neural population activity was recorded from areas relevant for grasp planning and execution: the anterior intraparietal area (AIP), F5 of the ventral premotor cortex, and the hand area of the primary motor cortex (M1). Grasp force was strongly encoded by neural populations of all three areas, thereby demonstrating for the first time the coding of grasp force in single- and multi-units of AIP. Neural coding of intended grasp force was most strongly represented in area F5. In addition to tuning analysis, a dimensionality reduction method revealed low-dimensional responses to grip type and grip force. Additionally, this method revealed a high correlation between latent variables of the neural population representing grasp force and the corresponding latent variables of electromyographic forearm muscle activity. Our results therefore suggest an important role of the cortical areas AIP, F5, and M1 in coding grasp force during movement execution as well as of F5 for coding intended grasp force.
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    • Journal Article

      Peri-hand space expands beyond reach in the context of walk-and-reach movements 

      Berger, Michael; Neumann, Peter; Gail, Alexander
      Scientific Reports 2019; 9(1): Art. 3013
      The brain incorporates sensory information across modalities to be able to interact with our environment. The peripersonal space (PPS), defined by a high level of crossmodal interaction, is centered on the relevant body part, e.g. the hand, but can spatially expand to encompass tools or reach targets during goal-directed behavior. Previous studies considered expansion of the PPS towards goals within immediate or tool-mediated reach, but not the translocation of the body as during walking. Here, we used the crossmodal congruency effect (CCE) to quantify the extension of the PPS and test if PPS can also expand further to include far located walk-and-reach targets accessible only by translocation of the body. We tested for orientation specificity of the hand-centered reference frame, asking if the CCE inverts with inversion of the hand orientation during reach. We show a high CCE with onset of the movement not only towards reach targets but also walk-and-reach targets. When participants must change hand orientation, the CCE decreases, if not vanishes, and does not simply invert. We conclude that the PPS can expand to the action space beyond immediate or tool-mediated reaching distance but is not purely hand-centered with respect to orientation.
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    • Journal Article

      Non-invasive genotyping with a massively parallel sequencing panel for the detection of SNPs in HPA-axis genes 

      Gutleb, D. R.; Ostner, J.; Schülke, O.; Wajjwalku, W.; Sukmak, M.; Roos, C.; Noll, A.
      Scientific Reports 2018; 8(1): Art. 15944
      We designed a genotyping panel for the investigation of the genetic underpinnings of inter-individual differences in aggression and the physiological stress response. The panel builds on single nucleotide polymorphisms (SNPs) in genes involved in the three subsystems of the hypothalamic-pituitary-adrenal (HPA)-axis: the catecholamine, serotonin and corticoid metabolism. To promote the pipeline for use with wild animal populations, we used non-invasively collected faecal samples from a wild population of Assamese macaques (Macaca assamensis). We targeted loci of 46 previously reported SNPs in 21 candidate genes coding for elements of the HPA-axis and amplified and sequenced them using next-generation Illumina sequencing technology. We compared multiple bioinformatics pipelines for variant calling and variant effect prediction. Based on this strategy and the application of different quality thresholds, we identified up to 159 SNPs with different types of predicted functional effects among our natural study population. This study provides a massively parallel sequencing panel that will facilitate integrating large-scale SNP data into behavioural and physiological studies. Such a multi-faceted approach will promote understanding of flexibility and constraints of animal behaviour and hormone physiology.
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    • Journal Article

      Functional analysis of potential cleavage sites in the MERS-coronavirus spike protein 

      Kleine-Weber, Hannah; Elzayat, Mahmoud Tarek; Hoffmann, Markus; Pöhlmann, Stefan
      Scientific Reports 2018; 8(1): Art. 16597
      The Middle East respiratory syndrome-related coronavirus (MERS-CoV) can cause severe disease and has pandemic potential. Therefore, development of antiviral strategies is an important task. The activation of the viral spike protein (S) by host cell proteases is essential for viral infectivity and the responsible enzymes are potential therapeutic targets. The cellular proteases furin, cathepsin L and TMPRSS2 can activate MERS-S and may cleave the S protein at two distinct sites, termed S1/S2 and S2'. Moreover, a potential cathepsin L cleavage site in MERS-S has been reported. However, the relative importance of these sites for MERS-S activation is incompletely understood. Here, we used mutagenic analysis and MERS-S-bearing vectors to study the contribution of specific cleavage sites to S protein-driven entry. We found that an intact S1/S2 site was only required for efficient entry into cells expressing endogenous TMPRSS2. In keeping with a previous study, pre-cleavage at the S1/S2 motif (RSVR) was important although not essential for subsequent MERS-S activation by TMPRSS2, and indirect evidence was obtained that this motif is processed by a protease depending on an intact RXXR motif, most likely furin. In contrast, the S2' site (RSAR) was required for robust viral entry into all cell lines tested and the integrity of one of the two arginines was sufficient for efficient entry. These findings suggest that cleavage at S2' is carried out by proteases recognizing a single arginine, most likely TMPRSS2 and cathepsin L. Finally, mutation of the proposed cathepsin L site did not impact viral entry and double mutation of S1/S2 and S2' site was compatible with cathepsin L- but not TMPRSS2-dependent host cell entry, indicating that cathepsin L can process the S protein at auxiliary sites. Collectively, our results indicate a rigid sequence requirement for S protein activation by TMPRSS2 but not cathepsin L.
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    • Journal Article

      Clarifying and expanding the social complexity hypothesis for communicative complexity 

      Peckre, Louise; Kappeler, Peter M.; Fichtel, Claudia
      Behavioral Ecology and Sociobiology 2019; 73(11)
      Variation in communicative complexity has been conceptually and empirically attributed to social complexity, with animals living in more complex social environments exhibiting more signals and/or more complex signals than animals living in simpler social environments.As compelling as studies highlighting a link between social and communicative variables are, this hypothesis remains challenged by operational problems, contrasting results, and several weaknesses of the associated tests. Specifically, how to best operationalize social and communicative complexity remains debated; alternative hypotheses, such as the role of a species’ ecology, morphology, or phylogenetic history, have been neglected; and the actual ways in which variation in signaling is directly affected by social factors remain largely unexplored. In this review, we address these three issues and propose an extension of the Bsocial complexity hypothesis for communicative complexity^ that resolves and acknowledges the above factors.We specifically argue for integrating the inherently multimodal nature of communication into a more comprehensive framework and for acknowledging the social context of derived signals and the potential of audience effects. By doing so, we believe it will be possible to generate more accurate predictions about which specific social parameters may be responsible for selection on new or more complex signals, as well as to uncover potential adaptive functions that are not necessarily apparent from studying communication in only one modality.
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    • Journal Article

      Human lung tissue provides highly relevant data about efficacy of new anti-asthmatic drugs 

      Danov, Olga; Jiménez Delgado, Sharon Melissa; Obernolte, Helena; Seehase, Sophie; Dehmel, Susann; Braubach, Peter; Fieguth, Hans-Gerd; Matschiner, Gabriele; Fitzgerald, Mary; Jonigk, Danny; et al.
      Knauf, SaschaPfennig, OlafWarnecke, GregorWichmann, JudyBraun, ArminSewald, Katherina
      PlOS ONE 2018; 13(11): Art. e0207767
      Subgroups of patients with severe asthma are insensitive to inhaled corticosteroids and require novel therapies on top of standard medical care. IL-13 is considered one of the key cytokines in the asthma pathogenesis, however, the effect of IL-13 was mostly studied in rodents. This study aimed to assess IL-13 effect in human lung tissue for the development of targeted therapy approaches such as inhibition of soluble IL-13 or its receptor IL-4Rα subunit. Precision-cut lung slices (PCLS) were prepared from lungs of rodents, non-human primates (NHP) and humans. Direct effect of IL-13 on human lung tissue was observed on inflammation, induction of mucin5AC, and airway constriction induced by methacholine and visualized by videomicroscopy. Anti-inflammatory treatment was evaluated by co-incubation of IL-13 with increasing concentrations of IL-13/IL-13 receptor inhibitors. IL-13 induced a two-fold increase in mucin5AC secretion in human bronchial tissue. Additionally, IL-13 induced release of proinflammatory cytokines eotaxin-3 and TARC in human PCLS. Anti-inflammatory treatment with four different inhibitors acting either on the IL-13 ligand itself (anti-IL-13 antibody, similar to Lebrikizumab) or the IL-4Rα chain of the IL-13/IL-4 receptor complex (anti-IL-4Rα #1, similar to AMG 317, and #2, similar to REGN668) and #3 PRS-060 (a novel anticalin directed against this receptor) could significantly attenuate IL-13 induced inflammation. Contrary to this, IL-13 did not induce airway hyperresponsiveness (AHR) in human and NHP PCLS, although it was effective in rodent PCLS. Overall, this study demonstrates that IL-13 stimulation induces production of mucus and biomarkers of allergic inflammation in human lung tissue ex-vivo but no airway hyperresponsiveness. The results of this study show a more distinct efficacy than known from animals models and a clear discrepancy in AHR induction. Moreover, it allows a translational approach in inhibitor profiling in human lung tissue.
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    • Journal Article

      A system for production of defective interfering particles in the absence of infectious influenza A virus 

      Bdeir, Najat; Arora, Prerna; Gärtner, Sabine; Hoffmann, Markus; Reichl, Udo; Pöhlmann, Stefan; Winkler, Michael
      PlOS ONE 2019; 14(3): Art. e0212757
      Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy.
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    • Journal Article

      Diagnosing Zika virus infection against a background of other flaviviruses: Studies in high resolution serological analysis. 

      Hansen, Sören; Hotop, Sven-Kevin; Faye, Oumar; Ndiaye, Oumar; Böhlken-Fascher, Susanne; Pessôa, Rodrigo; Hufert, Frank; Stahl-Hennig, Christiane; Frank, Ronald; Czerny, Claus-Peter; et al.
      Schmidt-Chanasit, JonasSanabani, Sabri S.Sall, Amadou A.Niedrig, MatthiasBrönstrup, MarkFritz, Hans-JoachimAbd El Wahed, Ahmed
      Scientific Reports 2019; 9(1): Art. 3648
      Zika virus (ZIKV) is a mosquito-borne flavivirus. Homologous proteins of different flaviviruses display high degrees of sequence identity, especially within subgroups. This leads to extensive immunological cross-reactivity and corresponding problems for developing a ZIKV-specific serological assay. In this study, peptide microarrays were employed to identify individual ZIKV antibody targets with promise in differential diagnosis. A total of 1643 overlapping oligopeptides were synthesized and printed onto glass slides. Together, they encompass the full amino acid sequences of ZIKV proteomes of African, Brazilian, USA, and French Polynesian origins. The resulting ZIKV scanning microarray chips were used to screen three pools of sera from recent Zika outbreaks in Senegal and Cape Verde, in Brazil, and from overseas travelers returning to the EU. Together with a mixed pool of well characterized, archived sera of patients suffering from infections by dengue, yellow fever, tick-borne encephalitis, and West Nile viruses, a total of 42 sera went into the study. Sixty-eight antibody target regions were identified. Most of which were hitherto unknown. Alignments and sequence comparisons revealed 13 of which could be classified as bona fide ZIKV-specific. These identified antibody target regions constitute a founding set of analytical tools for serological discrimination of ZIKV from other flaviviruses.
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    • Journal Article

      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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    • Journal Article

      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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    • Journal Article

      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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    • Journal Article

      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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    • Journal Article

      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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