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  • Journal Article

    Complementary encoding of priors in monkey frontoparietal network supports a dual process of decision-making 

    Suriya-Arunroj, Lalitta; Gail, Alexander
    eLife 2019; 8: Art. e47581
    Prior expectations of movement instructions can promote preliminary action planning and influence choices. We investigated how action priors affect action-goal encoding in premotor and parietal cortices and if they bias subsequent free choice. Monkeys planned reaches according to visual cues that indicated relative probabilities of two possible goals. On instructed trials, the reach goal was determined by a secondary cue respecting these probabilities. On rarely interspersed free-choice trials without instruction, both goals offered equal reward. Action priors induced graded free-choice biases and graded frontoparietal motor-goal activity, complementarily in two subclasses of neurons. Down-regulating neurons co-encoded both possible goals and decreased opposite-to-preferred responses with decreasing prior, possibly supporting a process of choice by elimination. Up-regulating neurons showed increased preferred-direction responses with increasing prior, likely supporting a process of computing net likelihood. Action-selection signals emerged earliest in down-regulating neurons of premotor cortex, arguing for an initiation of selection in the frontal lobe.
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  • Journal Article

    Establishing an infrastructure for collaboration in primate cognition research 

    Altschul, Drew M.; Beran, Michael J.; Bohn, Manuel; Call, Josep; DeTroy, Sarah; Duguid, Shona J.; Egelkamp, Crystal L.; Fichtel, Claudia; Fischer, Julia; Flessert, Molly; et al.
    Hanus, DanielHaun, Daniel B. M.Haux, Lou M.Hernandez-Aguilar, R. AdrianaHerrmann, EstherHopper, Lydia M.Joly, MarineKano, FumihiroKeupp, StefanieMelis, Alicia P.Motes Rodrigo, AlbaRoss, Stephen R.Sánchez-Amaro, AlejandroSato, YutaroSchmitt, VanessaSchweinfurth, Manon K.Seed, Amanda M.Taylor, DerryVölter, Christoph J.Warren, ElizabethWatzek, Julia
    PLOS ONE 2019; 14(10): Art. e0223675
    Inferring the evolutionary history of cognitive abilities requires large and diverse samples. However, such samples are often beyond the reach of individual researchers or institutions, and studies are often limited to small numbers of species. Consequently, methodological and site-specific-differences across studies can limit comparisons between species. Here we introduce the ManyPrimates project, which addresses these challenges by providing a large-scale collaborative framework for comparative studies in primate cognition. To demonstrate the viability of the project we conducted a case study of short-term memory. In this initial study, we were able to include 176 individuals from 12 primate species housed at 11 sites across Africa, Asia, North America and Europe. All subjects were tested in a delayed-response task using consistent methodology across sites. Individuals could access food rewards by remembering the position of the hidden reward after a 0, 15, or 30-second delay. Overall, individuals performed better with shorter delays, as predicted by previous studies. Phylogenetic analysis revealed a strong phylogenetic signal for short-term memory. Although, with only 12 species, the validity of this analysis is limited, our initial results demonstrate the feasibility of a large, collaborative open-science project. We present the ManyPrimates project as an exciting opportunity to address open questions in primate cognition and behaviour with large, diverse datasets.
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  • Journal Article

    Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques 

    Winkler, Michael; Gärtner, Sabine; Markus, Lara; Hoffmann, Markus; Nehlmeier, Inga; Krawczak, Michael; Sauermann, Ulrike; Pöhlmann, Stefan
    PLOS ONE 2019; 14(11): Art. e0224082
    The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.
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  • Journal Article

    Estimating seed dispersal distance: A comparison of methods using animal movement and plant genetic data on two primate‐dispersed Neotropical plant species 

    Gelmi‐Candusso, Tiziana A.; Bialozyt, Ronald; Slana, Darja; Zárate Gómez, Ricardo; Heymann, Eckhard W.; Heer, Katrin
    Ecology and Evolution 2019; 9(16) p.8965-8977
    Seed dispersal distance (SDD) critically influences the survival of seedlings, spatial patterns of genetic diversity within plant populations, and gene flow among plant populations. In animal-dispersed species, foraging behavior and movement patterns determine SDD. Direct observations of seed dispersal events by animals in natural plant populations are mostly constrained by the high mobility and low visibility of seed dispersers. Therefore, diverse alternative methods are used to estimate seed dispersal distance, but direct comparisons of these approaches within the same seed dispersal system are mostly missing.We investigated two plant species with different life history traits, Leonia cymosa and Parkia panurensis, exclusively dispersed by two tamarin species, Saguinus mystax and Leontocebus nigrifrons. We compared SDD estimates obtained from direct observations, genetic identification of mother plants from seed coats, parentage analysis of seedlings/saplings, and phenomenological and mechanistic modeling approaches.SDD derived from the different methods ranged between 158 and 201 m for P. panurensis and between 178 and 318 m for L. cymosa. In P. panurensis, the modeling approaches resulted in moderately higher estimates than observations and genotyping of seed coats. In L. cymosa, parentage analysis resulted in a lower estimate than all other methods. Overall, SDD estimates for P. panurensis (179 ± 16 m; mean ± SD) were significantly lower than for L. cymosa (266 ± 59 m; mean ± SD).Differences among methods were related to processes of the seed dispersal loop integrated by the respective methods (e.g., seed deposition or seedling distribution). We discuss the merits and limitations of each method and highlight the aspects to be considered when comparing SDD derived from different methodologies. Differences among plant species were related to differences in reproductive traits influencing gut passage time and feeding behavior, highlighting the importance of plant traits on animal-mediated seed dispersal distance.
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  • Journal Article

    Analysis of Resistance of Ebola Virus Glycoprotein-Driven Entry Against MDL28170, An Inhibitor of Cysteine Cathepsins 

    Hoffmann, Markus; Kaufmann, Svenja Victoria; Fischer, Carina; Maurer, Wiebke; Moldenhauer, Anna-Sophie; Pöhlmann, Stefan
    Pathogens 2019; 8(4): Art. 192
    Ebola virus (EBOV) infection can cause severe and frequently fatal disease in human patients. The EBOV glycoprotein (GP) mediates viral entry into host cells. For this, GP depends on priming by the pH-dependent endolysosomal cysteine proteases cathepsin B (CatB) and, to a lesser degree, cathepsin L (CatL), at least in most cell culture systems. However, there is limited information on whether and how EBOV-GP can acquire resistance to CatB/L inhibitors. Here, we addressed this question using replication-competent vesicular stomatitis virus bearing EBOV-GP. Five passages of this virus in the presence of the CatB/CatL inhibitor MDL28170 were su cient to select resistant viral variants and sequencing revealed that all GP sequences contained a V37A mutation, which, in the context of native GP, is located in the base of the GP surface unit. In addition, some GP sequences harbored mutation S195R in the receptor-binding domain. Finally, mutational analysis demonstrated that V37A but not S195R conferred resistance against MDL28170 and other CatB/CatL inhibitors. Collectively, a single amino acid substitution in GP is su cient to confer resistance against CatB/CatL inhibitors, suggesting that usage of CatB/CatL inhibitors for antiviral therapy may rapidly select for resistant viral variants.
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  • Journal Article

    Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein 

    Voigt, Kathleen; Hoffmann, Markus; Drexler, Jan Felix; Müller, Marcel Alexander; Drosten, Christian; Herrler, Georg; Krüger, Nadine
    Viruses 2019; 11(9): Art. 800
    The Ghana virus (GhV) is phylogenetically related to the zoonotic henipaviruses Nipah (NiV) and Hendra virus. Although GhV uses the highly conserved receptor ephrin-B2, the fusogenicity is restricted to cell lines of bat origin. Furthermore, the surface expression of the GhV attachment glycoprotein (G) is reduced compared to NiV and most of this protein is retained in the endoplasmic reticulum (ER). Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). We demonstrate that neither the cytoplasmic tail nor the transmembrane domain is responsible for the intracellular retention of GhV G. Furthermore, the cytoplasmic tail of GhV G modulates the fusogenicity of GhV F and therefore controls the species-restricted fusogenicity of the GhV surface glycoproteins.
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  • Journal Article

    Strain diversity of Treponema pallidum subsp. pertenue suggests rare interspecies transmission in African nonhuman primates 

    Chuma, Idrissa S.; Roos, Christian; Atickem, Anagaw; Bohm, Torsten; Anthony Collins, D.; Grillová, Linda; Hallmaier-Wacker, Luisa K.; Kazwala, Rudovick R.; Keyyu, Julius D.; Lüert, Simone; et al.
    Maloueki, UlrichOppelt, JanPetrželková, Klára J.Piel, AlexanderStewart, Fiona A.Šmajs, DavidKnauf, Sascha
    Scientific Reports 2019; 9(1): Art. 14243
    In our most recent study, we found that in Tanzania infection with Treponema pallidum (TP) subsp. pertenue (TPE) is present in four different monkey species. In order to gain information on the diversity and epidemiological spread of the infection in Tanzanian nonhuman primates (NHP), we identified two suitable candidate genes for multi-locus sequence typing (MLST). We demonstrate the functionality of the MLST system in invasively and non-invasively collected samples. While we were not able to demonstrate frequent interspecies transmission of TPE in Tanzanian monkeys, our results show a clustering of TPE strains according to geography and not host species, which is suggestive for rare transmission events between different NHP species. In addition to the geographic stability, we describe the relative temporal stability of the strains infecting NHPs and identified multi-strain infection. Differences between TPE strains of NHP and human origin are highlighted. Our results show that antibiotic resistance does not occur in Tanzanian TPE strains of NHP origin.
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  • Journal Article

    Perspective review of optical imaging in welfare assessment in animal-based research 

    Pereira, Carina Barbosa; Kunczik, Janosch; Bleich, André; Haeger, Christine; Kiessling, Fabian; Thum, Thomas; Tolba, René; Lindauer, Ute; Treue, Stefan; Czaplik, Michael
    Journal of Biomedical Optics 2019; 24: Art. 070601
    To refine animal research, vital signs, activity, stress, and pain must be monitored. In chronic studies, some measures can be assessed using telemetry sensors. Although this methodology provides high-precision data, an initial surgery for device implantation is necessary, potentially leading to stress, wound infections, and restriction of motion. Recently, camera systems have been adapted for animal research. We give an overview of parameters that can be assessed using imaging in the visible, near-infrared, and thermal spectrum of light. It focuses on heart activity, respiration, oxygen saturation, and motion, as well as on wound analysis. For each parameter, we offer recommendations on the minimum technical requirements of appropriate systems, regions of interest, and light conditions, among others. In general, these systems demonstrate great performance. For heart and respiratory rate, the error was <4  beats  /  min and 5 breaths/min. Furthermore, the systems are capable of tracking animals during different behavioral tasks. Finally, studies indicate that inhomogeneous temperature distribution around wounds might be an indicator of (pending) infections. In sum, camera-based techniques have several applications in animal research. As vital parameters are currently only assessed in sedated animals, the next step should be the integration of these modalities in home-cage monitoring.
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  • Journal Article

    Spider Monkeys in Human-Modified Landscapes 

    Arroyo-Rodríguez, Víctor; Pérez-Elissetche, Gloria Karina; Ordóñez-Gómez, José D.; González-Zamora, Arturo; Chaves, Óscar M.; Sánchez-López, Sònia; Chapman, Colin A.; Morales-Hernández, Karenina; Pablo-Rodríguez, Miriam; Ramos-Fernández, Gabriel
    Tropical Conservation Science 2016; 10 p.1-13
    With the extant of tropical forest degradation, primates increasingly inhabit forest patches embedded in anthropogenic matrices. Such matrices are composed of different land cover types (e.g., agricultural lands and cattle pastures), but large uncertainty remains about the ability of primates to use these land covers. Here, we assessed the use of the landscape matrix by spider monkeys (Ateles geoffroyi) in 13 forest sites from three countries (Mexico, Costa Rica, and El Salvador). Based on ad libitum records from >212 months of field observations, we found that spider monkeys used four types of land covers for feeding or traveling: secondary vegetation, isolated trees, tree crops, and vegetation corridors. Secondary vegetation was more frequently used than the other land covers. The number of land covers present in the matrix was positively related to the number of land covers used for traveling and feeding. Monkeys consumed 53 plant species in the matrix, mostly native and old-growth or late-successional forest species, although they also used three cultivated tree species. Most species were trees, especially from preferred food species, although monkeys also used palms, lianas, and shrubs. Monkeys fed principally from fruits, but they also used leaves, wood, and flowers. Most species were used from secondary vegetation and isolated trees. These findings suggest that the landscape matrix can provide supplementary food sources for this endangered primate and opportunities for traveling (i.e., spatial connectivity) in human-modified landscapes—information that can be used to improve conservation strategies, especially under the context of land-sharing management strategies (e.g., agroforestry).
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  • Journal Article

    Highly variable lifespan in an annual reptile, Labord’s chameleon (Furcifer labordi) 

    Eckhardt, Falk; Kappeler, Peter M.; Kraus, Cornelia
    Scientific Reports 2017; 7(1)
    Among tetrapods, the current record holder for shortest lifespan is Labord's chameleon, Furcifer labordi. These reptiles from the arid southwest of Madagascar have a reported lifespan of 4-5 months during the annual rainy season and spend the majority of their life (8-9 months) as a developing embryo. This semelparous, annual life history is unique among tetrapods, but only one population (Ranobe) in the southernmost distribution range has been studied. We therefore investigated the potential for environmentally-dependent variability in lifespan in a population in Kirindy Forest, which has a much longer warm rainy season. While no adults were found after March in Ranobe, the disappearance of adults was delayed by several months in Kirindy. Our data also revealed sex-biased mortality, suggesting that females have a longevity advantage. Furthermore, we found that, after an unusually long previous rainy season, one female was capable of surviving until a second breeding season. Keeping F. labordi in cages under ambient conditions demonstrated that also males can also survive until the next season of activity under these conditions. Our study therefore revealed considerable variability in the extreme life history of this tetrapod that is linked to variation in ecological factors.
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  • Journal Article

    Strategic deployment of feature-based attentional gain in primate visual cortex 

    Kozyrev, Vladislav; Daliri, Mohammad Reza; Schwedhelm, Philipp; Treue, Stefan
    PLOS Biology 2019; 17(8): Art. e3000387
    Attending to visual stimuli enhances the gain of those neurons in primate visual cortex that preferentially respond to the matching locations and features (on-target gain). Although this is well suited to enhance the neuronal representation of attended stimuli, it is nonoptimal under difficult discrimination conditions, as in the presence of similar distractors. In such cases, directing attention to neighboring neuronal populations (off-target gain) has been shown to be the most efficient strategy, but although such a strategic deployment of attention has been shown behaviorally, its underlying neural mechanisms are unknown. Here, we investigated how attention affects the population responses of neurons in the middle temporal (MT) visual area of rhesus monkeys to bidirectional movement inside the neurons' receptive field (RF). The monkeys were trained to focus their attention onto the fixation spot or to detect a direction or speed change in one of the motion directions (the "target"), ignoring the distractor motion. Population activity profiles were determined by systematically varying the patterns' directions while maintaining a constant angle between them. As expected, the response profiles show a peak for each of the 2 motion directions. Switching spatial attention from the fixation spot into the RF enhanced the peak representing the attended stimulus and suppressed the distractor representation. Importantly, the population data show a direction-dependent attentional modulation that does not peak at the target feature but rather along the slopes of the activity profile representing the target direction. Our results show that attentional gains are strategically deployed to optimize the discriminability of target stimuli, in line with an optimal gain mechanism proposed by Navalpakkam and Itti.
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  • Journal Article

    Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance 

    Korniy, Natalia; Goyal, Akanksha; Hoffmann, Markus; Samatova, Ekaterina; Peske, Frank; Pöhlmann, Stefan; Rodnina, Marina V.
    Nucleic Acids Research 2019; 47(10) p.5210-5222
    A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a -1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNALeu that reads the UUA codon at the mRNA slippery site. This tRNALeu isoacceptor is particularly rare in human cell lines derived from T-lymphocytes, the cells that are targeted by HIV-1. When UUA decoding is delayed, the frameshifting follows an alternative route, which maintains the Gag to Gag-Pol ratio constant. A second potential slippery site downstream of the first one is normally inefficient but can also support -1-frameshifting when altered by a compensatory resistance mutation in response to current antiviral drug therapy. Together these different regimes allow the virus to maintain a constant -1-frameshifting efficiency to ensure successful virus propagation.
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  • Journal Article

    Long-tailed macaques extract statistical information from repeated types of events to make rational decisions under uncertainty 

    Placì, Sarah; Padberg, Marie; Rakoczy, Hannes; Fischer, Julia
    Scientific Reports 2019; 9(1): Art. 12107
    Human children and apes seem to be intuitive statisticians when making predictions from populations of objects to randomly drawn samples, whereas monkeys seem not to be. Statistical reasoning can also be investigated in tasks in which the probabilities of different possibilities must be inferred from relative frequencies of events, but little is known about the performance of nonhuman primates in such tasks. In the current study, we investigated whether long-tailed macaques extract statistical information from repeated types of events to make predictions under uncertainty. In each experiment, monkeys first experienced the probability of rewards associated with different factors separately. In a subsequent test trial, monkeys could then choose between the different factors presented simultaneously. In Experiment 1, we tested whether long-tailed macaques relied on probabilities and not on a comparison of absolute quantities to make predictions. In Experiment 2 and 3 we varied the nature of the predictive factors and the complexity of the covariation structure between rewards and factors. Results indicate that long-tailed macaques extract statistical information from repeated types of events to make predictions and rational decisions under uncertainty, in more or less complex scenarios. These findings suggest that the presentation format affects the monkeys' statistical reasoning abilities.
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  • Journal Article

    Routing information flow by separate neural synchrony frequencies allows for “functionally labeled lines” in higher primate cortex 

    Khamechian, Mohammad Bagher; Kozyrev, Vladislav; Treue, Stefan; Esghaei, Moein; Daliri, Mohammad Reza
    Proceedings of the National Academy of Sciences 2019; 116(25) p.12506-12515
    Efficient transfer of sensory information to higher (motor or associative) areas in primate visual cortical areas is crucial for transforming sensory input into behavioral actions. Dynamically increasing the level of coordination between single neurons has been suggested as an important contributor to this efficiency. We propose that differences between the functional coordination in different visual pathways might be used to unambiguously identify the source of input to the higher areas, ensuring a proper routing of the information flow. Here we determined the level of coordination between neurons in area MT in macaque visual cortex in a visual attention task via the strength of synchronization between the neurons' spike timing relative to the phase of oscillatory activities in local field potentials. In contrast to reports on the ventral visual pathway, we observed the synchrony of spikes only in the range of high gamma (180 to 220 Hz), rather than gamma (40 to 70 Hz) (as reported previously) to predict the animal's reaction speed. This supports a mechanistic role of the phase of high-gamma oscillatory activity in dynamically modulating the efficiency of neuronal information transfer. In addition, for inputs to higher cortical areas converging from the dorsal and ventral pathway, the distinct frequency bands of these inputs can be leveraged to preserve the identity of the input source. In this way source-specific oscillatory activity in primate cortex can serve to establish and maintain "functionally labeled lines" for dynamically adjusting cortical information transfer and multiplexing converging sensory signals.
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  • Journal Article

    One size fits all? Relationships among group size, health, and ecology indicate a lack of an optimal group size in a wild lemur population 

    Rudolph, Katja; Fichtel, Claudia; Schneider, Dominik; Heistermann, Michael; Koch, Flávia; Daniel, Rolf; Kappeler, Peter M.
    Behavioral Ecology and Sociobiology 2019; 73(9): Art. 132
    Group size is a key component of sociality and can affect individual health and fitness. However, proximate links explaining this relationship remain poorly understood, partly because previous studies neglected potential confounding effects of ecological factors. Here, we correlated group size with various measures of health while controlling for measures of seasonality and habitat quality, to explore trade-offs related to group living in a mainly folivorous primate—Verreaux’s sifakas (Propithecus verreauxi). Over a course of 2 years, we studied 42 individuals of 7 differently sized groups (range 2–10) and combined measures of faecal glucocorticoid metabolites (n > 2300 samples), parasitism (n > 500 samples), ranging and activity patterns, together with estimates of habitat quality (measures of ~ 7000 feeding trees). None of our measures was correlated with group size, while seasonality, but not habitat quality, impacted almost all examined variables. We conclude that group size alone might be insufficient to explain patterns in the sociality-health nexus or that the small range of group sizes in this species does not induce effects suggested for species living in larger groups. An optimal group size balancing the advantages and disadvantages of living in differently sized groups may not exist for Verreaux’s sifakas. Our results do not support predictions of the ecological constraints hypothesis or the optimal group size hypothesis as they may only account for species limited in group size by ecological factors—a condition that may not apply to the majority of folivorous mammals, which seem to be limited by social factors.
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  • Journal Article

    Small Neotropical primates promote the natural regeneration of anthropogenically disturbed areas 

    Heymann, Eckhard W.; Culot, Laurence; Knogge, Christoph; Smith, Andrew C.; Tirado Herrera, Emérita R.; Müller, Britta; Stojan-Dolar, Mojca; Lledo Ferrer, Yvan; Kubisch, Petra; Kupsch, Denis; et al.
    Slana, DarjaKoopmann, Mareike LenaZiegenhagen, BirgitBialozyt, RonaldMengel, ChristinaHambuckers, JulienHeer, Katrin
    Scientific Reports 2019; 9(1): Art. 10356
    Increasingly large proportions of tropical forests are anthropogenically disturbed. Where natural regeneration is possible at all, it requires the input of plant seeds through seed dispersal from the forest matrix. Zoochorous seed dispersal - the major seed dispersal mode for woody plants in tropical forests - is particularly important for natural regeneration. In this study, covering a period of more than 20 years, we show that small New World primates, the tamarins Saguinus mystax and Leontocebus nigrifrons, increase their use of an anthropogenically disturbed area over time and disperse seeds from primary forest tree species into this area. Through monitoring the fate of seeds and through parentage analyses of seedlings of the legume Parkia panurensis from the disturbed area and candidate parents from the primary forest matrix, we show that tamarin seed dispersal is effective and contributes to the natural regeneration of the disturbed area.
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  • Journal Article

    Is implicit Theory of Mind real but hard to detect? Testing adults with different stimulus materials 

    Kulke, Louisa; Wübker, Marieke; Rakoczy, Hannes
    Royal Society Open Science 2019; 6(7): Art. 190068
    Recently, Theory of Mind (ToM) research has been revolutionized by new methods. Eye-tracking studies measuring subjects' looking times or anticipatory looking have suggested that implicit and automatic forms of ToM develop much earlier in ontogeny than traditionally assumed and continue to operate outside of subjects’ awareness throughout the lifespan. However, the reliability of these implicit methods has recently been put into question by an increasing number of non-replications. What remains unclear from these accumulating non-replication findings, though, is whether they present true negatives (there is no robust phenomenon of automatic ToM) or false ones (automatic ToM is real but difficult to tap). In order to address these questions, the current study implemented conceptual replications of influential anticipatory looking ToM tasks with a new variation in the stimuli. In two separate preregistered studies, we used increasingly realistic stimuli and controlled for potential confounds. Even with these more realistic stimuli, previous results could not be replicated. Rather, the anticipatory looking pattern found here remained largely compatible with more parsimonious explanations. In conclusion, the reality and robustness of automatic ToM remains controversial.
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  • Journal Article

    Pro-Angiogenic Macrophage Phenotype to Promote Myocardial Repair 

    Ferraro, Bartolo; Leoni, Giovanna; Hinkel, Rabea; Ormanns, Steffen; Paulin, Nicole; Ortega-Gomez, Almudena; Viola, Joana R.; de Jong, Renske; Bongiovanni, Dario; Bozoglu, Tarik; et al.
    Maas, Sanne L.D’Amico, MicheleKessler, ThorstenZeller, TanjaHristov, MichaelReutelingsperger, ChrisSager, Hendrik B.Döring, YvonneNahrendorf, MatthiasKupatt, ChristianSoehnlein, Oliver
    Journal of the American College of Cardiology 2019; 73(23) p.2990-3002
    BACKGROUND: Heart failure following myocardial infarction (MI) remains one of the major causes of death worldwide, and its treatment is a crucial challenge of cardiovascular medicine. An attractive therapeutic strategy is to stimulate endogenous mechanisms of myocardial regeneration. OBJECTIVES: This study evaluates the potential therapeutic treatment with annexin A1 (AnxA1) to induce cardiac repair after MI. METHODS: AnxA1 knockout (AnxA1-/-) and wild-type mice underwent MI induced by ligation of the left anterior descending coronary artery. Cardiac functionality was assessed by longitudinal echocardiographic measurements. Histological, fluorescence-activated cell sorting, dot blot analysis, and in vitro/ex vivo studies were used to assess the myocardial neovascularization, macrophage content, and activity in response to AnxA1. RESULTS: AnxA1-/- mice showed a reduced cardiac functionality and an expansion of proinflammatory macrophages in the ischemic area. Cardiac macrophages from AnxA1-/- mice exhibited a dramatically reduced ability to release the proangiogenic mediator vascular endothelial growth factor (VEGF)-A. However, AnxA1 treatment enhanced VEGF-A release from cardiac macrophages, and its delivery in vivo markedly improved cardiac performance. The positive effect of AnxA1 treatment on cardiac performance was abolished in wild-type mice transplanted with bone marrow derived from Cx3cr1creERT2Vegfflox/flox or in mice depleted of macrophages. Similarly, cardioprotective effects of AnxA1 were obtained in pigs in which full-length AnxA1 was overexpressed by use of a cardiotropic adeno-associated virus. CONCLUSIONS: AnxA1 has a direct action on cardiac macrophage polarization toward a pro-angiogenic, reparative phenotype. AnxA1 stimulated cardiac macrophages to release high amounts of VEGF-A, thus inducing neovascularization and cardiac repair.
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  • Journal Article

    Future Directions for Personality Research: Contributing New Insights to the Understanding of Animal Behavior 

    Wilson, Vanessa; Guenther, Anja; Øverli, Øyvind; Seltmann, Martin W.; Altschul, Drew
    Animals 2019; 9(5): Art. 240
    As part of the European Conference on Behavioral Biology 2018, we organized a symposium entitled, "Animal personality: providing new insights into behavior?" The aims of this symposium were to address current research in the personality field, spanning both behavioral ecology and psychology, to highlight the future directions for this research, and to consider whether differential approaches to studying behavior contribute something new to the understanding of animal behavior. In this paper, we discuss the study of endocrinology and ontogeny in understanding how behavioral variation is generated and maintained, despite selection pressures assumed to reduce this variation. We consider the potential mechanisms that could link certain traits to fitness outcomes through longevity and cognition. We also address the role of individual differences in stress coping, mortality, and health risk, and how the study of these relationships could be applied to improve animal welfare. From the insights provided by these topics, we assert that studying individual differences through the lens of personality has provided new directions in behavioral research, and we encourage further research in these directions, across this interdisciplinary field.
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  • Journal Article

    Species-Specific Conservation of Linear Antigenic Sites on Vaccinia Virus A27 Protein Homologs of Orthopoxviruses 

    Ahsendorf, Henrike; Gan, Li; Eltom, Kamal; Abd El Wahed, Ahmed; Hotop, Sven-Kevin; Roper, Rachel; Beutling, Ulrike; Broenstrup, Mark; Stahl-Hennig, Christiane; Hoelzle, Ludwig; et al.
    Czerny, Claus-Peter
    Viruses 2019; 11(6): Art. 493
    The vaccinia virus (VACV) A27 protein and its homologs, which are found in a large number of members of the genus Orthopoxvirus (OPXV), are targets of viral neutralization by host antibodies. We have mapped six binding sites (epitopes #1A: aa 32-39, #1B: aa 28-33, #1C: aa 26-31, #1D: 28-34, #4: aa 9-14, and #5: aa 68-71) of A27 specific monoclonal antibodies (mAbs) using peptide arrays. MAbs recognizing epitopes #1A-D and #4 neutralized VACV Elstree in a complement dependent way (50% plaque-reduction: 12.5-200 µg/mL). Fusion of VACV at low pH was blocked through inhibition of epitope #1A. To determine the sequence variability of the six antigenic sites, 391 sequences of A27 protein homologs available were compared. Epitopes #4 and #5 were conserved among most of the OPXVs, while the sequential epitope complex #1A-D was more variable and, therefore, responsible for species-specific epitope characteristics. The accurate and reliable mapping of defined epitopes on immuno-protective proteins such as the A27 of VACV enables phylogenetic studies and insights into OPXV evolution as well as to pave the way to the development of safer vaccines and chemical or biological antivirals.
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