Conflict resolution in socially housed Sumatran orangutans (Pongo abelii)

Background Peaceful conflict resolution strategies have been identified as effective mechanisms for minimising the potential costs of group life in many gregarious species, especially in primates. The knowledge of conflict-management in orangutans, though, is still extremely limited. Given their semi-solitary lives in the wild, there seems to be barely a need for orangutans to apply conflict management strategies other than avoidance. However, because of the rapid loss of orangutan habitat due to deforestation, opportunities to prevent conflicts by dispersion are shrinking. Additionally, more and more orangutans are brought into rehabilitation centres where they are bound to live in close contact with conspecifics. This raises the questions of whether and how orangutans are able to cope with conflicts, which are inevitably connected with group life. Methods Observational zoo-studies provide a valuable method to investigate such potential: in zoos, orangutans usually live in permanent groups and face the challenges of group life every day. Therefore, we observed a group of six socially-housed Sumatran orangutans at the Dortmund Zoo, Germany, both in their spacious outdoor enclosure in the summer and in the less spacious indoor enclosure in the winter. During 157.5 h of observation, we collected data on aggressive interactions, third-party interventions and post-conflict affiliations. We applied the post-conflict/matched-control observation (PC/MC) and the time rule method to investigate the occurrence of reconciliation and post-conflict third-party affiliations. Results We recorded a total of 114 aggressive interactions (including conflicts in the context of weaning and of male sexual coercion). As expected, we found an increase of both open conflicts and peaceful conflict resolution under less spacious conditions. In accordance with previous reports, we observed interventions by initially uninvolved individuals. Whereas we found no clear evidence for post-conflict third-party affiliations, we were able to demonstrate the occurrence of reconciliation among orangutans. Discussion Notwithstanding the small sample size and the explorative character of our study, we found evidence that orangutans possess a potential for prosocial conflict resolution. When living in groups and under conditions in which dispersion is no longer an option, orangutans are capable to flexibly apply strategies of conflict resolution to cease open conflicts and to repair the potential social damage of aggressive interactions. These strategies are similar to those of other great apes

Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci

This is an Open Access article. © 2015 The Author(s). Published by Springer Berlin Heidelberg.The susceptibility of 12 field-collected isolates and 4 laboratory strains of cat fleas, Ctenocephalides felis was determined by topical application of some of the insecticides used as on-animal therapies to control them. In the tested field-collected flea isolates the LD50 values for fipronil and imidacloprid ranged from 0.09 to 0.35 ng/flea and 0.02 to 0.19 ng/flea, respectively, and were consistent with baseline figures published previously. The extent of variation in response to four pyrethroid insecticides differed between compounds with the LD50 values for deltamethrin ranging from 2.3 to 28.2 ng/flea, etofenprox ranging from 26.7 to 86.7 ng/flea, permethrin ranging from 17.5 to 85.6 ng/flea, and d-phenothrin ranging from 14.5 to 130 ng/flea. A comparison with earlier data for permethrin and deltamethrin implied a level of pyrethroid resistance in all isolates and strains. LD50 values for tetrachlorvinphos ranged from 20.0 to 420.0 ng/flea. The rdl mutation (conferring target-site resistance to cyclodiene insecticides) was present in most field-collected and laboratory strains, but had no discernible effect on responses to fipronil, which acts on the same receptor protein as cyclodienes. The kdr and skdr mutations conferring target-site resistance to pyrethroids but segregated in opposition to one another, precluding the formation of genotypes homozygous for both mutations.Peer reviewedFinal Published versio

Brain structure and function: a multidisciplinary pipeline to study hominoid brain evolution

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains

Sourcing high tissue quality brains from deceased wild primates with known socio‐ecology

The selection pressures that drove dramatic encephalisation processes through the mammal lineage remain elusive, as does knowledge of brain structure reorganisation through this process. In particular, considerable structural brain changes are present across the primate lineage, culminating in the complex human brain that allows for unique behaviours such as language and sophisticated tool use. To understand this evolution, a diverse sample set of humans' closest relatives with varying socio-ecologies is needed. However, current brain banks predominantly curate brains from primates that died in zoological gardens. We try to address this gap by establishing a field pipeline mitigating the challenges associated with brain extractions of wild primates in their natural habitat. The success of our approach is demonstrated by our ability to acquire a novel brain sample of deceased primates with highly variable socio-ecological exposure and a particular focus on wild chimpanzees. Methods in acquiring brain tissue from wild settings are comprehensively explained, highlighting the feasibility of conducting brain extraction procedures under strict biosafety measures by trained veterinarians in field sites. Brains are assessed at a fine-structural level via high-resolution MRI and state-of-the-art histology. Analyses confirm that excellent tissue quality of primate brains sourced in the field can be achieved with a comparable tissue quality of brains acquired from zoo-living primates. Our field methods are noninvasive, here defined as not harming living animals, and may be applied to other mammal systems than primates. In sum, the field protocol and methodological pipeline validated here pose a major advance for assessing the influence of socio-ecology on medium to large mammal brains, at both macro- and microstructural levels as well as aiding with the functional annotation of brain regions and neuronal pathways via specific behaviour assessments.Output Status: Forthcoming/Available Online Additional authors: Richard McElreath, Alfred Anwander, Philipp Gunz, Markus Morawski, Angela D. Friederici, Nikolaus Weiskopf, Fabian H. Leendertz, Roman M. Wittig EBC Cosortium: Karoline Albig, Bala Amarasekaran, Sam Angedakin, Alfred Anwander, Daniel Aschoff, Caroline Asiimwe, Laurent Bailanda, Jacinta C. Beehner, Raphael Belais, Thore J. Bergman, Birgit Blazey, Andreas Bernhard, Christian Bock, Pénélope Carlier, Julian Chantrey, Catherine Crockford, Tobias Deschner, Ariane Düx1, Luke Edwards, Cornelius Eichner, Géraldine Escoubas2, Malak Ettaj, Karina Flores, Richard Francke, Angela D. Friederici, Cédric Girard-Buttoz, Jorge Gomez Fortun, Zoro Bertin GoneBi, Tobias Gräßle, Eva Gruber-Dujardin, Philipp Gunz, Jess Hartel, Daniel B. M. Haun, Michael Henshall, Catherine Hobaiter, Noémie Hofman, Jenny E. Jaffe, Carsten Jäger, Anna Jauch, Stomy Kahemere, Evgeniya Kirilina, Robert Klopfleisch, Tobias Knauf-Witzens, Kathrin S. Kopp, Guy Landry Mamboundou Kouima, Bastian Lange, Kevin Langergraber, Arne Lawrenz, Fabian H. Leendertz, Ilona Lipp, Matys Liptovszky, Tobias Loubser Theron, Christelle Patricia Lumbu, Patrice Makouloutou Nzassi, Kerstin Mätz-Rensing, Richard McElreath, Matthew McLennan, Zoltan Mezö, Sophie Moittie, Torsten Møller, Markus Morawski, David Morgan, Timothy Mugabe, Martin Muller, Matthias Müller, Inoussa Njumboket, Karin Olofsson-Sannö, Alain Ondzie, Emily Otali, Michael Paquette, Simone Pika, Kerrin Pine, Andrea Pizarro, Kamilla Pléh, Jessica Rendel, Sandra Reichler-Danielowski, Martha M. Robbins, Alejandra Romero Forero, Konstantin Ruske, Liran Samuni, Crickette Sanz, André Schüle, Ingo Schwabe, Katarina Schwalm, Sheri Speede, Lara Southern, Jonas Steiner, Marc Stidworthy, Martin Surbeck, Claudia Szentiks, Tanguy Tanga, Reiner Ulrich, Steve Unwin, Erica van de Waal, Sue Walker, Nikolaus Weiskopf, Gudrun Wibbelt, Roman M. Wittig, Kim Wood, Klaus Zuberbühle

Sourcing high tissue quality brains from deceased wild primates with known socio‐ecology

The selection pressures that drove dramatic encephalisation processes through the mammal lineage remain elusive, as does knowledge of brain structure reorganisation through this process. In particular, considerable structural brain changes are present across the primate lineage, culminating in the complex human brain that allows for unique behaviours such as language and sophisticated tool use. To understand this evolution, a diverse sample set of humans' closest relatives with varying socio-ecologies is needed. However, current brain banks predominantly curate brains from primates that died in zoological gardens. We try to address this gap by establishing a field pipeline mitigating the challenges associated with brain extractions of wild primates in their natural habitat. The success of our approach is demonstrated by our ability to acquire a novel brain sample of deceased primates with highly variable socio-ecological exposure and a particular focus on wild chimpanzees. Methods in acquiring brain tissue from wild settings are comprehensively explained, highlighting the feasibility of conducting brain extraction procedures under strict biosafety measures by trained veterinarians in field sites. Brains are assessed at a fine-structural level via high-resolution MRI and state-of-the-art histology. Analyses confirm that excellent tissue quality of primate brains sourced in the field can be achieved with a comparable tissue quality of brains acquired from zoo-living primates. Our field methods are noninvasive, here defined as not harming living animals, and may be applied to other mammal systems than primates. In sum, the field protocol and methodological pipeline validated here pose a major advance for assessing the influence of socio-ecology on medium to large mammal brains, at both macro- and microstructural levels as well as aiding with the functional annotation of brain regions and neuronal pathways via specific behaviour assessments

Tamoxifen-Induced Cre-loxP Recombination Is Prolonged in Pancreatic Islets of Adult Mice

Tamoxifen (Tm)-inducible Cre recombinases are widely used to perform gene inactivation and lineage tracing studies in mice. Although the efficiency of inducible Cre-loxP recombination can be easily evaluated with reporter strains, the precise length of time that Tm induces nuclear translocation of CreERTm and subsequent recombination of a target allele is not well defined, and difficult to assess. To better understand the timeline of Tm activity in vivo, we developed a bioassay in which pancreatic islets with a Tm-inducible reporter (from Pdx1PB-CreERTm;R26RlacZ mice) were transplanted beneath the renal capsule of adult mice previously treated with three doses of 1 mg Tm, 8 mg Tm, or corn oil vehicle. Surprisingly, recombination in islet grafts, as assessed by expression of the β-galactosidase (β-gal) reporter, was observed days or weeks after Tm treatment, in a dose-dependent manner. Substantial recombination occurred in islet grafts long after administration of 3×8 mg Tm: in grafts transplanted 48 hours after the last Tm injection, 77.9±0.4% of β-cells were β-gal+; in β-cells placed after 1 week, 46.2±5.0% were β-gal+; after 2 weeks, 26.3±7.0% were β-gal+; and after 4 weeks, 1.9±0.9% were β-gal+. Islet grafts from mice given 3×1 mg Tm showed lower, but notable, recombination 48 hours (4.9±1.7%) and 1 week (4.5±1.9%) after Tm administration. These results show that Tm doses commonly used to induce Cre-loxP recombination may continue to label significant numbers of cells for weeks after Tm treatment, possibly confounding the interpretation of time-sensitive studies using Tm-dependent models. Therefore, investigators developing experimental approaches using Tm-inducible systems should consider both maximal recombination efficiency and the length of time that Tm-induced Cre-loxP recombination occurs

The Adaptor Molecule Nck Localizes the WAVE Complex to Promote Actin Polymerization during CEACAM3-Mediated Phagocytosis of Bacteria

Background: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF) Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. Principal Findings: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. Conclusions: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment

Sox9-Haploinsufficiency Causes Glucose Intolerance in Mice

The HMG box transcription factor Sox9 plays a critical role in progenitor cell expansion during pancreas organogenesis and is required for proper endocrine cell development in the embryo. Based on in vitro studies it has been suggested that Sox9 controls expression of a network of important developmental regulators, including Tcf2/MODY5, Hnf6, and Foxa2, in pancreatic progenitor cells. Here, we sought to: 1) determine whether Sox9 regulates this transcriptional network in vivo and 2) investigate whether reduced Sox9 gene dosage leads to impaired glucose homeostasis in adult mice. Employing two genetic models of temporally-controlled Sox9 inactivation in pancreatic progenitor cells, we demonstrate that contrary to in vitro findings, Sox9 is not required for Tcf2, Hnf6, or Foxa2 expression in vivo. Moreover, our analysis revealed a novel role for Sox9 in maintaining the expression of Pdx1/MODY4, which is an important transcriptional regulator of beta-cell development. We further show that reduced beta-cell mass in Sox9-haploinsufficient mice leads to glucose intolerance during adulthood. Sox9-haploinsufficient mice displayed 50% reduced beta-cell mass at birth, which recovered partially via a compensatory increase in beta-cell proliferation early postnatally. Endocrine islets from mice with reduced Sox9 gene dosage exhibited normal glucose stimulated insulin secretion. Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. Glucose intolerance in Sox9-haploinsufficient mice suggests that mutations in Sox9 could play a role in diabetes in humans

Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders

COUP-TFII Controls Mouse Pancreatic β-Cell Mass through GLP-1-β-Catenin Signaling Pathways

Background: The control of the functional pancreatic beta-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how beta-cell mass is determined