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Inter-specific emotion recognition is especially adaptive when species spend a long time in close association, like dogs and humans. Here, we comprehensively studied the human ability to recognize facial expressions associated with dog emotions (hereafter, emotions). Participants were presented with pictures of dogs, humans and chimpanzees, showing angry, fearful, happy, neutral and sad emotions, and had to assess which emotion was shown, and the context in which the picture had been taken. Participants were recruited among children and adults with different levels of general experience with dogs, resulting from different personal (i.e. dog ownership) and cultural experiences (i.e. growing up or being exposed to a cultural milieu in which dogs are highly valued and integrated in human lives). Our results showed that some dog emotions such as anger and happiness are recognized from early on, independently of experience. However, the ability to recognize dog emotions is mainly acquired through experience. In adults, the probability of recognizing dog emotions was higher for participants grown up in a cultural milieu with a positive attitude toward dogs, which may result in different passive exposure, interest or inclination toward this species. Methods - Participants - Materials - Procedures - Statistics Results - Model 1 - Children - Model 2 - Adults - Speraman exact tests Discussion

ATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved in pathways triggering cough and may contribute to the pathophysiology of endometriosis and overactive bladder. However, despite the strong therapeutic rationale for targeting P2X3 receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer. Here we present a P2X3 receptor antagonist, eliapixant (BAY 1817080), which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3. We show that eliapixant reduces inflammatory pain in relevant animal models. We also provide the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation, a phenomenon hypothesised to contribute to several diseases, including endometriosis. To test whether eliapixant could help treat endometriosis, we confirmed P2X3 expression on nerve fibers innervating human endometriotic lesions. We then demonstrate that eliapixant reduces vaginal hyperalgesia in an animal model of endometriosis-associated dyspareunia, even beyond treatment cessation. Our findings indicate that P2X3 antagonism could alleviate pain, including non-menstrual pelvic pain, and modify the underlying disease pathophysiology in women with endometriosis. Eliapixant is currently under clinical development for the treatment of disorders associated with hypersensitive nerve fibers.

Most current knowledge about dogs’ understanding of, and reacting to, their environment is limited to the visual or auditory modality, but it remains unclear how olfaction and cognition are linked together. Here we investigate how domestic dogs search for their owners using their excellent olfactory sense. We raise the question whether dogs have a representation of someone when they smell their track. The question is what they expect when they follow a trail or whether they perceive an odour as a relevant or non-relevant stimulus. We adopted a classical violation-of-expectation paradigm—and as targets we used two persons that were both important to the dog, usually the owners. In the critical condition subjects could track the odour trail of one target, but at the end of the trail they find another target. Dogs showed an increased activity when the person did not correspond with the trail compared to a control condition. Moreover, we found huge individual differences in searching behaviour supporting the assumption that dogs are only able to smell when they really sniff, and that the temperature has an influence on dogs performance. Results are discussed in the light of how cognitive abilities, motivation and odour perception influence each other. Methods - Subjects. - Setup. - Procedure. - Design. - Coding and analysis. Results Discussion

Multicellular organisms can be regarded as metaorganisms, comprising of a macroscopic host interacting with associated microorganisms. Within this alliance, the host has to ensure attracting beneficial bacteria and defending against pathogens to establish and maintain a healthy homeostasis. Here, we obtained several lines of evidence arguing that Aurelia aurita uses interference with bacterial quorum sensing (QS) - quorum quenching (QQ) - as one host defense mechanism. Three A. aurita-derived proteins interfering with bacterial QS were identified by functionally screening a metagenomic library constructed from medusa-derived mucus. Native expression patterns of these host open reading frames (ORFs) differed in the diverse life stages (associated with different microbiota) pointing to a specific role in establishing the developmental stage-specific microbiota. Highly increased expression of all QQ-ORFs in germ-free animals further indicates their impact on the microbiota. Moreover, incubation of native animals with pathogenic bacteria induced expression of the identified QQ-ORFs arguing for a host defense strategy against confronting bacteria by interference with bacterial QS. In agreement, immobilized recombinant QQ proteins induced restructuring of polyp-associated microbiota through changing abundance and operational taxonomic unit composition. Thus, we hypothesize that additional to the immune system host-derived QQ-activities potentially control bacterial colonization.

Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-β dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-β dependent cell differentiation.

The non-isotropic alignment of molecules can increase the interaction efficiency with propagating light fields. This applies to both emissive and absorptive systems and can be exploited for achieving unprecedented efficiencies of organic opto-electronic devices such as organic light-emitting diodes. Optical analysis has revealed certain phosphorescent emitters to align spontaneously in an advantageous orientation. Unfortunately, established approaches only determine an average orientation because emission patterns solely depend on the second moments of the transition dipole vector distribution. In order to resolve further details of such a distribution, additional differences in the emission characteristics of parallel and perpendicularly oriented emitters need to be introduced. A thin metal layer near the emitters introduces plasmon mediated losses mostly for perpendicular emitters. Then, analyzing the emission at different polarizations allows one to measure emission lifetimes of mostly parallel or mostly perpendicular oriented emitters. This should alter the transient emission when observing the temporal phosphorescence decay under different directions and/or polarizations. The angular width of the orientation distribution can be derived from the degree of such lifetime splitting. Our results suggest a narrow but obliquely oriented molecular ensemble of Ir(MDQ)2(acac) doped into the α-NPD host inside an Organic LED stack.

Mycoses induced by C.albicans or A.fumigatus can cause important host damage either by deficient or exaggerated immune response. Regulation of chemokine and cytokine signaling plays a crucial role for an adequate inflammation, which can be modulated by vitamins A and D. Non-coding RNAs (ncRNAs) as transcription factors or cis-acting antisense RNAs are known to be involved in gene regulation. However, the processes during fungal infections and treatment with vitamins in terms of therapeutic impact are unknown. We show that in monocytes both vitamins regulate ncRNAs involved in amino acid metabolism and immune system processes using comprehensive RNA-Seq analyses. Compared to protein-coding genes, fungi and bacteria induced an expression change in relatively few ncRNAs, but with massive fold changes of up to 4000. We defined the landscape of long-ncRNAs (lncRNAs) in response to pathogens and observed variation in the isoforms composition for several lncRNA following infection and vitamin treatment. Most of the involved antisense RNAs are regulated and positively correlated with their sense protein-coding genes. We investigated lncRNAs with stimulus specific immunomodulatory activity as potential marker genes: LINC00595, SBF2-AS1 (A.fumigatus) and RP11-588G21.2, RP11-394l13.1 (C.albicans) might be detectable in the early phase of infection and serve as therapeutic targets in the future.

Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment.

The non-isotropic alignment of molecules can increase the interaction efficiency with propagating light fields. This applies to both emissive and absorptive systems and can be exploited for achieving unprecedented efficiencies of organic opto-electronic devices such as organic light-emitting diodes. Optical analysis has revealed certain phosphorescent emitters to align spontaneously in an advantageous orientation. Unfortunately, established approaches only determine an average orientation because emission patterns solely depend on the second moments of the transition dipole vector distribution. In order to resolve further details of such a distribution, additional differences in the emission characteristics of parallel and perpendicularly oriented emitters need to be introduced. A thin metal layer near the emitters introduces plasmon mediated losses mostly for perpendicular emitters. Then, analyzing the emission at different polarizations allows one to measure emission lifetimes of mostly parallel or mostly perpendicular oriented emitters. This should alter the transient emission when observing the temporal phosphorescence decay under different directions and/or polarizations. The angular width of the orientation distribution can be derived from the degree of such lifetime splitting. Our results suggest a narrow but obliquely oriented molecular ensemble of Ir(MDQ)2(acac) doped into the α-NPD host inside an Organic LED stack.