Low resting metabolic rate and increased hunger due to ß-MSH and ß-endorphin deletion in a canine model.

Mutations that perturb leptin-melanocortin signaling are known to cause hyperphagia and obesity, but energy expenditure has not been well studied outside rodents. We report on a common canine mutation in pro-opiomelanocortin (POMC), which prevents production of ß-melanocyte-stimulating hormone (ß-MSH) and ß-endorphin but not α-MSH; humans, similar to dogs, produce α-MSH and ß-MSH from the POMC propeptide, but rodents produce only α-MSH. We show that energy expenditure is markedly lower in affected dogs, which also have increased motivational salience in response to a food cue, indicating increased wanting or hunger. There was no difference in satiety at a modified ad libitum meal or in their hedonic response to food, nor disruption of adrenocorticotropic hormone (ACTH) or thyroid axes. In vitro, we show that ß-MSH signals comparably to α-MSH at melanocortin receptors. These data implicate ß-MSH and ß-endorphin as important in determining hunger and moderating energy expenditure and suggest that this role is independent of the presence of α-MSH.

The Zoomorphic Miro Robot's Affective Expression Design and Perceived Appearance.

This article proposes design guidelines for 11 affective expressions for the Miro robot, and evaluates the expressions through an online video study with 116 participants. All expressions were recognized significantly above the chance level. For six of the expressions, the correct response was selected significantly more than the others, while more than one emotion was associated to some other expressions. Design decisions and the robot's limitations that led to selecting other expressions, along with the correct expression, are discussed. We also investigated how participants' abilities to recognize human and animal emotions, their tendency to anthropomorphize, and their familiarity with and attitudes towards animals and pets might have influenced the recognition of the robot's affective expressions. Results show significant impact of human emotion recognition, difficulty in understanding animal emotions, and anthropomorphism tendency on recognition of Robot's expressions. We did not find such effects regarding familiarity with/attitudes towards animals/pets in terms of how they influenced participants' recognition of the designed affective expressions. We further studied how the robot is perceived in general and showed that it is mostly perceived to be gender neutral, and, while it is often associated with a dog or a rabbit, it can also be perceived as a variety of other animals.

Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro).

Starting from the MLPCN probe compound ML300, a structure-based optimization campaign was initiated against the recent severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CLpro). X-ray structures of SARS-CoV-1 and SARS-CoV-2 3CLpro enzymes in complex with multiple ML300-based inhibitors, including the original probe ML300, were obtained and proved instrumental in guiding chemistry toward probe compound 41 (CCF0058981). The disclosed inhibitors utilize a noncovalent mode of action and complex in a noncanonical binding mode not observed by peptidic 3CLpro inhibitors. In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes. Antiviral activity was established using a SARS-CoV-2-infected Vero E6 cell viability assay and a plaque formation assay. Compound 41 demonstrates nanomolar activity in these respective assays, comparable in potency to remdesivir. These findings have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.

Gaze-following behind barriers in domestic dogs.

Although gaze-following abilities have been demonstrated in a wide range of species, so far no clear evidence has been available for dogs. In the current study, we examined whether dogs follow human gaze behind an opaque barrier in two different contexts, in a foraging situation and in a non-foraging situation (food involved vs. food not involved in the situation). We assumed that dogs will spontaneously follow the human gaze and that the foraging context will have a positive effect on dogs' gaze-following behaviour by causing an expectation in the dogs that food might be hidden somewhere in the room and might be communicated by the experimenter. This expectation presumably positively affects their motivational and attentional state. Here, we report that dogs show evidence of spontaneous gaze-following behind barriers in both situations. According to our findings, the dogs gazed earlier at the barrier in the indicated direction in both contexts. However, as we expected, the context also has some effect on dogs' gaze-following behaviour, as more dogs gazed behind the barrier in the indicated direction in the foraging situation. The present results also support the idea that gaze-following is a characteristic skill in mammals which may more easily emerge in certain functional contexts.

Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

Sensing sociality in dogs: what may make an interactive robot social?

This study investigated whether dogs would engage in social interactions with an unfamiliar robot, utilize the communicative signals it provides and to examine whether the level of sociality shown by the robot affects the dogs' performance. We hypothesized that dogs would react to the communicative signals of a robot more successfully if the robot showed interactive social behaviour in general (towards both humans and dogs) than if it behaved in a machinelike, asocial way. The experiment consisted of an interactive phase followed by a pointing session, both with a human and a robotic experimenter. In the interaction phase, dogs witnessed a 6-min interaction episode between the owner and a human experimenter and another 6-min interaction episode between the owner and the robot. Each interaction episode was followed by the pointing phase in which the human/robot experimenter indicated the location of hidden food by using pointing gestures (two-way choice test). The results showed that in the interaction phase, the dogs' behaviour towards the robot was affected by the differential exposure. Dogs spent more time staying near the robot experimenter as compared to the human experimenter, with this difference being even more pronounced when the robot behaved socially. Similarly, dogs spent more time gazing at the head of the robot experimenter when the situation was social. Dogs achieved a significantly lower level of performance (finding the hidden food) with the pointing robot than with the pointing human; however, separate analysis of the robot sessions suggested that gestures of the socially behaving robot were easier for the dogs to comprehend than gestures of the asocially behaving robot. Thus, the level of sociality shown by the robot was not enough to elicit the same set of social behaviours from the dogs as was possible with humans, although sociality had a positive effect on dog-robot interactions.

Emotion attribution to a non-humanoid robot in different social situations.

In the last few years there was an increasing interest in building companion robots that interact in a socially acceptable way with humans. In order to interact in a meaningful way a robot has to convey intentionality and emotions of some sort in order to increase believability. We suggest that human-robot interaction should be considered as a specific form of inter-specific interaction and that human-animal interaction can provide a useful biological model for designing social robots. Dogs can provide a promising biological model since during the domestication process dogs were able to adapt to the human environment and to participate in complex social interactions. In this observational study we propose to design emotionally expressive behaviour of robots using the behaviour of dogs as inspiration and to test these dog-inspired robots with humans in inter-specific context. In two experiments (wizard-of-oz scenarios) we examined humans' ability to recognize two basic and a secondary emotion expressed by a robot. In Experiment 1 we provided our companion robot with two kinds of emotional behaviour ("happiness" and "fear"), and studied whether people attribute the appropriate emotion to the robot, and interact with it accordingly. In Experiment 2 we investigated whether participants tend to attribute guilty behaviour to a robot in a relevant context by examining whether relying on the robot's greeting behaviour human participants can detect if the robot transgressed a predetermined rule. Results of Experiment 1 showed that people readily attribute emotions to a social robot and interact with it in accordance with the expressed emotional behaviour. Results of Experiment 2 showed that people are able to recognize if the robot transgressed on the basis of its greeting behaviour. In summary, our findings showed that dog-inspired behaviour is a suitable medium for making people attribute emotional states to a non-humanoid robot.

Eighteen-month-old human infants show intensive development in comprehension of different types of pointing gestures.

This study explored children's development in comprehending four types of pointing gestures with different familiarity. Our aim was to highlight human infants' pointing comprehension abilities under the same conditions used for various animal species. Sixteen children were tested longitudinally in a two-choice task from 1 year of age. At the age of 12 and 14 months, infants did not exceed chance level with either of the gestures used. Infants were successful with distal pointing and long cross-pointing at the age of 16 months. By the age of 18 months, infants showed a high success rate with the less familiar gestures (forward cross-pointing and far pointing) as well. Their skills at this older age show close similarity with those demonstrated previously by dogs when using exactly the same testing procedures. Our longitudinal studies also revealed that in a few infants, the ability to comprehend pointing gestures is already apparent before 16 months of age. In general, we found large individual variation. This has been described for a variety of cognitive skills in human development and seems to be typical for pointing comprehension as well.

Comprehension and utilisation of pointing gestures and gazing in dog-human communication in relatively complex situations.

The aim of the present investigation was to study the visual communication between humans and dogs in relatively complex situations. In the present research, we have modelled more lifelike situations in contrast to previous studies which often relied on using only two potential hiding locations and direct association between the communicative signal and the signalled object. In Study 1, we have provided the dogs with four potential hiding locations, two on each side of the experimenter to see whether dogs are able to choose the correct location based on the pointing gesture. In Study 2, dogs had to rely on a sequence of pointing gestures displayed by two different experimenters. We have investigated whether dogs are able to recognise an 'indirect signal', that is, a pointing toward a pointer. In Study 3, we have examined whether dogs can understand indirect information about a hidden object and direct the owner to the particular location. Study 1 has revealed that dogs are unlikely to rely on extrapolating precise linear vectors along the pointing arm when relying on human pointing gestures. Instead, they rely on a simple rule of following the side of the human gesturing. If there were more targets on the same side of the human, they showed a preference for the targets closer to the human. Study 2 has shown that dogs are able to rely on indirect pointing gestures but the individual performances suggest that this skill may be restricted to a certain level of complexity. In Study 3, we have found that dogs are able to localise the hidden object by utilising indirect human signals, and they are able to convey this information to their owner.

Evolutionary approach to communication between humans and dogs.

Dog-human communication has been widely investigated recently for different theoretical reasons, in most cases through dogs' comprehension of human gestural cues. Dogs have been reported to be very skilful in comprehending a variety of human pointing gestures in many independent studies. This paper provides a short overview of the possible explanations behind the dogs' exceptional communicational abilities towards humans from an evolutionary perspective, concluding that the different and seemingly contradictory hypotheses are not exclusive but they might have a synergic effect.

A comparative approach to dogs' (Canis familiaris) and human infants' comprehension of various forms of pointing gestures.

We investigated whether dogs and 2-, and 3-year-old human infants living, in some respects, in very similar social environments are able to comprehend various forms of the human pointing gesture. In the first study, we looked at their ability to comprehend different arm pointing gestures (long cross-pointing, forward cross-pointing and elbow cross-pointing) to locate a hidden object. Three-year-olds successfully used all gestures as directional cues, while younger children and dogs could not understand the elbow cross-pointing. Dogs were also unsuccessful with the forward cross-pointing. In the second study, we used unfamiliar pointing gestures i.e. using a leg as indicator (pointing with leg, leg cross-pointing, pointing with knee). All subjects were successful with leg pointing gestures, but only older children were able to comprehend the pointing with knee. We suggest that 3-year-old children are able to rely on the direction of the index finger, and show the strongest ability to generalize to unfamiliar gestures. Although some capacity to generalize is also evident in younger children and dogs, especially the latter appear biased in the use of protruding body parts as directional signals.

A comparative study of the use of visual communicative signals in interactions between dogs (Canis familiaris) and humans and cats (Felis catus) and humans.

Dogs' (Canis familiaris) and cats' (Felis catus) interspecific communicative behavior toward humans was investigated. In Experiment 1, the ability of dogs and cats to use human pointing gestures in an object-choice task was compared using 4 types of pointing cues differing in distance between the signaled object and the end of the fingertip and in visibility duration of the given signal. Using these gestures, both dogs and cats were able to find the hidden food; there was no significant difference in their performance. In Experiment 2, the hidden food was made inaccessible to the subjects to determine whether they could indicate the place of the hidden food to a naive owner. Cats lacked some components of attention-getting behavior compared with dogs. The results suggest that individual familiarization with pointing gestures ensures high-level performance in the presence of such gestures; however, species-specific differences could cause differences in signaling toward the human.