Non-primate Mammals Research Articles

A coati conundrum: how variation in levels of arboreality influences gait mechanics among three musteloid species.

The gait characteristics associated with arboreal locomotion have been frequently discussed in the context of primate evolution, wherein they present as a trio of distinctive features: a diagonal-sequence, diagonal-couplet gait pattern; a protracted arm at forelimb touchdown; and a hindlimb-biased weight support pattern. The same locomotor characteristics have been found in the woolly opossum, a fine-branch arborealist similar in ecology to some small-bodied primates. To further our understanding of the functional link between arboreality and primate-like locomotion, we present comparative data collected in the laboratory for three musteloid taxa. Musteloidea represents an ecologically diverse superfamily spanning numerous locomotor specializations that includes the highly arboreal kinkajou (Potos flavus), mixed arboreal/terrestrial red pandas (Ailurus fulgens) and primarily terrestrial coatis (Nasua narica). This study applies a combined kinetic and kinematic approach to compare the locomotor behaviors of these three musteloid taxa, representing varying degrees of arboreal specialization. We observed highly arboreal kinkajous to share many locomotor traits with primates. In contrast, red pandas (mixed terrestrial/arborealist) showed gait characteristics found in most non-primate mammals. Coatis, however, demonstrated a unique combination of locomotor traits, combining a lateral-sequence, lateral-couplet gait pattern typical of long-legged, highly terrestrial mammals, varying degrees of arm protraction, and a hindlimb-biased weight support pattern typical of most primates and woolly opossums. We conclude that the three gait characteristics traditionally used to describe arboreal walking in primates can occur independently from one another and not necessarily as a suite of interdependent characteristics, a phenomenon that has been reported for some primates.

Serial visual reversal learning in captive black-handed spider monkeys, Ateles geoffroyi

Recent research suggests that socio-ecological factors such as dietary specialization and social complexity may be drivers of advanced cognitive skills among primates. Therefore, we assessed the ability of 12 black-handed spider monkeys (Ateles geoffroyi), a highly frugivorous platyrrhine primate with strong fission-fusion dynamics, to succeed in a serial visual reversal learning task. Using a two-alternative choice paradigm we first trained the animals to reliably choose a rewarded visual stimulus over a non-rewarded one. Upon reaching a pre-set learning criterion we then switched the reward values of the two stimuli and assessed if and how quickly the animals learned to reverse their choices, again to a pre-set learning criterion. This stimulus reversal procedure was then continued for a total of 80 sessions of 10 trials each. We found that the spider monkeys quickly learned to reliably discriminate between two simultaneously presented visual stimuli, that they succeeded in a visual reversal learning task, and that they displayed an increase in learning speed across consecutive reversals, suggesting that they are capable of serial reversal learning-set formation with visual cues. The fastest-learning individual completed five reversals within the 80 sessions. The spider monkeys outperformed most other primate and nonprimate mammal species tested so far on this type of cognitive task, including chimpanzees, with regard to their learning speed in both the initial learning task and in the first reversal task, suggesting a high degree of behavioral flexibility and inhibitory control. Our findings support the notion that socio-ecological factors such as dietary specialization and social complexity foster advanced cognitive skills in primates.

Alzheimer's Disease Neuropathological Change in Aged Non-Primate Mammals.

Human brain aging is characterized by the production and deposition of β-amyloid (Aβ) in the form of senile plaques and cerebral amyloid angiopathy and the intracellular accumulation of hyper-phosphorylated tau (Hp-tau) to form neurofibrillary tangles (NFTs) and dystrophic neurites of senile plaques. The process progresses for years and eventually manifests as cognitive impairment and dementia in a subgroup of aged individuals. Aβ is produced and deposited first in the neocortex in most aged mammals, including humans; it is usually not accompanied by altered behavior and cognitive impairment. Hp-tau is less frequent than Aβ pathology, and NFTs are rare in most mammals. In contrast, NFTs are familiar from middle age onward in humans; NFTs first appear in the paleocortex and selected brain stem nuclei. NFTs precede for decades or years Aβ deposition and correlate with dementia in about 5% of individuals at the age of 65 and 25% at the age of 85. Based on these comparative data, (a) Aβ deposition is the most common Alzheimer's disease neuropathological change (ADNC) in the brain of aged mammals; (b) Hp-tau is less common, and NFTs are rare in most aged mammals; however, NFTs are the principal cytoskeletal pathology in aged humans; (c) NFT in aged humans starts in selected nuclei of the brain stem and paleocortical brain regions progressing to the most parts of the neocortex and other regions of the telencephalon; (d) human brain aging is unique among mammalian species due to the early appearance and dramatic progression of NFTs from middle age onward, matching with cognitive impairment and dementia in advanced cases; (e) neither mammalian nor human brain aging supports the concept of the amyloid cascade hypothesis.

A Macrocyclic Tweezers-Shaped Receptor for the Biomimetic Recognition of the Gal(α1-3)Gal Disaccharide of the α-Gal Antigen.

The Gal(α1-3)Gal is the terminal disaccharide unit of the α-Gal epitope [Gal(α1-3)Gal(β1-4)GlcNAc], an exogenous antigenic determinant with several clinical implications, found in all non-primate mammals and in several dangerous pathogens, including certain protozoa and mycobacteria. Its absence in humans makes the α-Gal epitope an interesting target for several infectious diseases. Here we present the development of a macrocyclic tweezers-shaped receptor, resulting from the combination of the structural features of two predecessors belonging to the family of diaminocarbazole receptors, which exhibits binding properties in the low millimolar range toward the Gal(α1-3)Gal disaccharide of the α-Gal antigen.

Diet components associated with specific bacterial taxa shape overall gut community compositions in omnivorous African viverrids.

Gut bacterial communities provide flexibility to hosts during dietary changes. Despite the increasing number of studies exploring the associations between broader dietary guilds of mammalian hosts and their gut bacteria, it is generally unclear how diversity and variability in consumed diets link to gut bacterial taxa in wild non-primate mammals, particularly in omnivores. Here, we contribute to filling this gap by exploring consumed diets and gut bacterial community compositions with metabarcoding of faecal samples for two African mammals, Civettictis civetta and Genetta spp., from the family Viverridae. For each individual sample, we characterised bacterial communities and identified dietary taxa by sequencing vertebrate, invertebrate and plant markers. This led us to establish diet compositions that diverged from what has previously been found from visual identification methods. Specifically, while the two genera have been categorised into the same dietary guild, we detected more animal dietary items than plant items in C. civetta, while in Genetta spp., we observed the opposite. We further found that individuals with similar diets have similar gut bacterial communities within both genera. This association tended to be driven by specific links between dietary items and gut bacterial genera, rather than communities as a whole, implying diet-driven selection for specific gut microbes in individual wild hosts. Our findings underline the importance of molecular tools for improving characterisations of omnivorous mammalian diets and highlight the opportunities for simultaneously disentangling links between diets and gut symbionts. Such insights can inform robustness and flexibility in host-microbe symbioses to dietary change associated with seasonal and habitat changes.

Alpha-Gal, epitope responsible for allergy to red meat, in the Mediterranean tick Hyalomma lusitanicum.

Alpha-Gal/α-Gal is an oligosaccharide produced by non-primate mammals. Humans have developed an immune response mediated by anti-α-Gal antibodies that can trigger an allergic reaction and cause anaphylaxis. In recent years, cases of patients with delayed allergic reaction to mammalian meat have been reported worldwide. In Spain, these cases have been related to the species Ixodes ricinus L. (Ixodida: Ixodidae), whose distribution is located in the north of the country. In this work, the presence of α-Gal in water-soluble extracts from samples of salivary glands and digestive tracts of Hyalomma lusitanicum Koch (Ixodida: Ixodidae) both engorged and collected from vegetation were studied. The presence of that epitope was confirmed by the presence of reactive proteins of >250 kDa in both samples. The highest concentrations of α-Gal were detected in salivary glands. Neither sex nor diet influenced the concentration of α-Gal, which seems to indicate its endogenous production and its possible inoculation to the host during tick feeding.

ASICs mediate fast excitatory synaptic transmission for tactile discrimination

Tactile discrimination, the ability to differentiate objects' physical properties such as texture, shape, and edges, is essential for environmental exploration, social interaction, and early childhood development. This ability heavily relies on Merkel cell-neurite complexes (MNCs), the tactile end-organs enriched in the fingertips of humans and the whisker hair follicles of non-primate mammals. Although recent studies have advanced our knowledge on mechanical transduction in MNCs, it remains unknown how tactile signals are encoded at MNCs. Here, using rodent whisker hair follicles, we show that tactile signals are encoded at MNCs as fast excitatory synaptic transmission. This synaptic transmission is mediated by acid-sensing ion channels (ASICs) located on the neurites of MNCs, with protons as the principal transmitters. Pharmacological inhibition or genetic deletion of ASICs diminishes the tactile encoding at MNCs and impairs tactile discrimination in animals. Together, ASICs are required for tactile encoding at MNCs to enable tactile discrimination in mammals.

Mainly Visual Aspects of Emotional Laterality in Cognitively Developed and Highly Social Mammals-A Systematic Review.

Several studies have shown that emotions are asymmetrically represented in the human brain and have proposed three main models (the 'right hemisphere hypothesis', the 'approach-withdrawal hypothesis' and the 'valence hypothesis') that give different accounts of this emotional laterality. Furthermore, in recent years, many investigations have suggested that a similar emotional laterality may also exist in different animal taxa. However, results of a previous systematic review of emotional laterality in non-human primates have shown that some of these studies might be criticized from the methodological point of view and support only in part the hypothesis of a continuum in emotional laterality across vertebrates. The aim of the present review therefore consisted in trying to expand this survey to other cognitively developed and highly social mammals, focusing attention on mainly visual aspects of emotional laterality, in studies conducted on the animal categories of horses, elephants, dolphins and whales. The 35 studies included in the review took into account three aspects of mainly visual emotional laterality, namely: (a) visual asymmetries for positive/familiar vs. negative/novel stimuli; (b) lateral position preference in mother-offspring or other affiliative interactions; (c) lateral position preference in antagonistic interactions. In agreement with data obtained from human studies that have evaluated comprehension or expression of emotions at the facial or vocal level, these results suggest that a general but graded right-hemisphere prevalence in the processing of emotions can be found at the visual level in cognitively developed non-primate social mammals. Some methodological problems and some implications of these results for human psychopathology are briefly discussed.

Allergy to galactose-α-1,3-galactose (α-gal) – A case report

Introduction: Meat allergy represents 3-15% of food allergies in paediatrics and 3% in adults. Galactose-α-1,3-galactose (α-gal) is an allergen present in non-primate mammals’ meat, responsible for crossed reactions with cetuximab and gelatine. Case description: 62-year-old male patient was sent to an Immunoallergology outpatient clinic for acetylsalicylic acid desensitization. He reported reproducible anaphylactic reactions beginning 3 hours after red meat ingestion. Currently, the patient strictly avoids red meat. The investigation confirmed sensitization to red meat and α-gal. Discussion/Conclusions: α-gal allergy presents some uncommon characteristics: the trigger (oligosaccharide), IgE-mediated reaction with late-onset, and the association with previous tick bites, responsible for primary sensitization. Patients must avoid red meat and tick bites and have an emergency plan with an adrenalin auto-injector.

Cystic fibrosis transmembrane conductance regulator (CFTR)’s evolution revealed that its mutation causes cystic fibrosis

Cystic fibrosis ( CF ) is a hereditary disease that can lead to death, mainly caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ). These mutations exhibit varying mechanisms and severity levels, posing a challenge for understanding their impact. Here, we hypothesized that mutations occurring in functionally important, conserved regions of the CFTR protein might lead to more severe CF phenotypes, while mutations in other domains may be less harmful. To identify these crucial regions, we conducted a survey of amino acid substitutions in CFTR across primates and non-primate mammals. Intriguingly, we found that most naturally occurring substitutions clustered within two CFTR domains, which paradoxically lacked CF-causing mutations. In contrast, CF mutations in humans are mainly located in the relatively conserved regions of CFTR, namely transmembrane domain 1 ( TMD1) and nucleotide binding domain 1 ( NBD1 ). This study presents the distribution of naturally occurring substitutions, and our findings provides a unique perspective for inferring and predicting disease-causing genetic variations by analyzing evolutionary trends.

An ON-type direction-selective ganglion cell in primate retina

To maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze-stabilization mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behaviour is initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements1. However, ON-DSGCs have not yet been identified in the retina of primates, raising the possibility that this reflex is mediated by cortical visual areas. Here we mined single-cell RNA transcriptomic data from primate retina to identify a candidate ON-DSGC. We then combined two-photon calcium imaging, molecular identification and morphological analysis to reveal a population of ON-DSGCs in the macaque retina. The morphology, molecular signature and GABA (γ-aminobutyric acid)-dependent mechanisms that underlie direction selectivity in primate ON-DSGCs are highly conserved with those in other mammals. We further identify a candidate ON-DSGC in human retina. The presence of ON-DSGCs in primates highlights the need to examine the contribution of subcortical retinal mechanisms to normal and aberrant gaze stabilization in the developing and mature visual system.

Allergy to galactose-α-1,3-galactose (α-gal) – A case report

Introduction: Meat allergy represents 3-15% of food allergies in paediatrics and 3% in adults. Galactose-α-1,3-galactose (α-gal) is an allergen present in non-primate mammals’ meat, responsible for crossed reactions with cetuximab and gelatine. Case description: 62-year-old male patient was sent to an Immunoallergology outpatient clinic for acetylsalicylic acid desensitization. He reported reproducible anaphylactic reactions beginning 3 hours after red meat ingestion. Currently, the patient strictly avoids red meat. The investigation confirmed sensitization to red meat and α-gal. Discussion/Conclusions: α-gal allergy presents some uncommon characteristics: the trigger (oligosaccharide), IgE-mediated reaction with late-onset, and the association with previous tick bites, responsible for primary sensitization. Patients must avoid red meat and tick bites and have an emergency plan with an adrenalin auto-injector.

The inferior alveolar nerve and its relationship to the mandibular canal.

Previous work on the mandibular canal, mental foramen, and mandibular foramen has focused on humans and some other non-primate mammals (with small sample sizes), but little work has investigated the mandibular canal and inferior alveolar nerve (IAN) across primates. However, it is important to understand the relationship between the IAN and mandibular canal due to the IAN's close relationship to the teeth and mastication, and thus dietary adaptations. While it is assumed that most bony canals within the skull grow around and form to pre-existing nervous structures, this relationship has never been validated for the IAN and mandibular canal. MicroCT scans of 273 individuals (131 females, 134 males, and 8 unknown sex) from 68 primate species and three mammalian outgroups, and diceCT scans of 66 individuals (35 females, 23 males, and 8 unknown sex) from 33 primate species and the same mammalian outgroups were used to create 3D models of the IAN and mandibular canal from which cross-sectional areas were taken at various points on the structures. Using qualitative descriptions, phylogenetic generalized least squares analysis, and phylogenetic ANOVAs, we were able to establish three main conclusions: (1) the mandibular canal is most often not a defined canal within the mandible of primates, (2) when the canal can be identified, the IAN does not comprise most of the space within, and (3) there are significant relationships between the IAN and the corresponding canals, with most showing isometry and the mental foramen/nerve showing negative allometry.

A robust role for motor cortex.

The role of motor cortex in non-primate mammals remains unclear. More than a century of stimulation, anatomical and electrophysiological studies has implicated neural activity in this region with all kinds of movement. However, following the removal of motor cortex, rats retain most of their adaptive behaviors, including previously learned skilled movements. Here we revisit these two conflicting views of motor cortex and present a new behavior assay, challenging animals to respond to unexpected situations while navigating a dynamic obstacle course. Surprisingly, rats with motor cortical lesions show clear impairments facing an unexpected collapse of the obstacles, while showing no impairment with repeated trials in many motor and cognitive metrics of performance. We propose a new role for motor cortex: extending the robustness of sub-cortical movement systems, specifically to unexpected situations demanding rapid motor responses adapted to environmental context. The implications of this idea for current and future research are discussed.

A multi-tissue transcriptomic landscape of female mice in estrus and diestrus provides clues for precision medicine.

Female reproductive cycle, also known as menstrual cycle or estrous cycle in primate or non-primate mammals, respectively, dominates the reproductive processes in non-pregnant state. However, in addition to reproductive tissues, reproductive cycle could also perform global regulation because the receptors of two major female hormones fluctuating throughout the cycle, estrogen and progesterone, are widely distributed. Therefore, a multi-tissue gene expression landscape is in continuous demand for better understanding the systemic changes during the reproductive cycle but remains largely undefined. Here we delineated a transcriptomic landscape covering 15 tissues of C57BL/6J female mice in two phases of estrous cycle, estrus and diestrus, by RNA-sequencing. Then, a number of genes, pathways, and transcription factors involved in the estrous cycle were revealed. We found the estrous cycle could widely regulate the neuro-functions, immuno-functions, blood coagulation and so on. And behind the transcriptomic alteration between estrus and diestrus, 13 transcription factors may play important roles. Next, bioinformatics modeling with 1,263 manually curated gene signatures of various physiological and pathophysiological states systematically characterized the beneficial/deleterious effects brought by estrus/diestrus on individual tissues. We revealed that the estrous cycle has a significant effect on cardiovascular system (aorta, heart, vein), in which the anti-hypertensive pattern in aorta induced by estrus is one of the most striking findings. Inspired by this point, we validated that two hypotensive drugs, felodipine and acebutolol, could exhibit significantly enhanced efficacy in estrus than diestrus by mouse and rat experiments. Together, this study provides a valuable data resource for investigating reproductive cycle from a transcriptomic perspective, and presents models and clues for investigating precision medicine associated with reproductive cycle.

Paleo-immunology of human anti-carbohydrate antibodies preventing primate extinctions.

Two human natural anti-carbohydrate antibodies appeared in critical evolutionary events that brought primates and hominins to brink of extinction. The first is the anti-Gal antibody, produced in Old-World monkeys (OWM), apes and humans. It binds the carbohydrate-antigen 'α-gal epitope' (Galα1-3Galβ1-4GlcNAc-R) on carbohydrate-chains (glycans) synthesized by non-primate mammals, lemurs and New-World monkeys (NWM). The second is anti-N-glycolylneuraminic-acid (anti-Neu5Gc) antibody binding Neu5Gc on glycans synthesized by OWM, apes and most non-primate mammals. Ancestral OWM and apes synthesized α-gal epitopes and were eliminated ~20-30 million-years-ago (mya). Only few accidentally mutated offspring lacking α-gal epitopes, produced anti-Gal and survived. Hominin-populations living ~3 mya synthesized Neu5Gc and were eliminated, but few mutated offspring that accidently lost their ability to synthesize Neu5Gc, produced natural anti-Neu5Gc antibody. These hominins survived and ultimately evolved into present-day humans. It is argued that these two near-extinction events were likely to be the result of epidemics caused by highly virulent and lethal enveloped viruses that killed parental-populations. These viruses presented α-gal epitopes or Neu5Gc synthesized in host-cells of the parental-populations. Mutated offspring survived the epidemics because they were protected from the lethal virus by the natural anti-Gal or anti-Neu5Gc antibodies they produced due to loss of immune-tolerance to α-gal epitopes or to Neu5Gc, respectively.

Interspecific Contagious Yawning in Humans

Contagious yawning, or the reflexive tendency to yawn following the detection of yawning in others, is well-documented among humans and a growing number of social vertebrates. While the most common form of yawn contagion occurs between conspecifics, some non-human animals in captivity have been reported to yawn in response to yawns from human handlers/caregivers. The current research sought to provide the first formal investigation of whether people yawn contagiously in response to yawns from non-human animals. In addition, this study aimed to test whether this response was modulated by phylogenetic relatedness and domestication/social closeness. A total of 296 participants from Amazon Mechanical Turk self-reported on their yawning behavior following exposure to a (1) control (non-yawning) condition or a compilation of yawning stimuli either from (2) fish, (3) amphibians, (4) reptiles, (5) birds, (6) non-primate mammals, (7) apes, or (8) domesticated cats and dogs. The results provide strong support for interspecific yawn contagion. However, neither the propensity to yawn (binary) nor total yawn frequency varied significantly across interspecific conditions. Overall, these findings suggest that the mechanisms governing yawn contagion can be activated by varied forms of yawning stimuli, including those from distantly related and unfamiliar species.

Multimodal anatomy of the human forniceal commissure

Ambiguity surrounds the existence and morphology of the human forniceal commissure. We combine advanced in-vivo tractography, multidirectional ex-vivo fiber dissection, and multiplanar histological analysis to characterize this structure’s anatomy. Across all 178 subjects, in-vivo fiber dissection based on the Human Connectome Project 7 T MRI data identifies no interhemispheric connections between the crura fornicis. Multidirectional ex-vivo fiber dissection under the operating microscope demonstrates the psalterium as a thin soft-tissue membrane spanning between the right and left crus fornicis, but exposes no commissural fibers. Multiplanar histological analysis with myelin and Bielchowsky silver staining, however, visualizes delicate cruciform fibers extending between the crura fornicis, enclosed by connective tissue, the psalterium. The human forniceal commissure is therefore much more delicate than previously described and presented in anatomical textbooks. This finding is consistent with the observed phylogenetic trend of a reduction of the forniceal commissure in non-human primates compared to non-primate eutherian mammals.

Reactivity to heparin in patients with alpha-gal allergy: A potential role for skin testing?

Galactose-alpha-1,3-galactose (alpha-gal) syndrome is an immunoglobulin (Ig)E-mediated allergy syndrome to an oligosaccharide found in nonprimate mammalian meat and mammalian-derived products.1 Oral consumption reactions are characteristically delayed, but are immediate with parenteral administration.1 Since the discovery of alpha-gal IgE antibodies while investigating hypersensitivity reactions to cetuximab, much attention has been paid to both theoretical risks and reported cases of hypersensitivity reactions to various medications and medical devices derived from nonprimate mammals.

Perspectives on Antiphonal Calling, Duetting and Counter-Singing in Non-primate Mammals: An Overview With Notes on the Coordinated Vocalizations of Bamboo Rats (Dactylomys spp., Rodentia: Echimyidae)

Temporally coordinated interactive vocalizations are important means of communication between individuals in various animal taxa. In mammals, interactive calling and singing can be highly synchronized to create either overlapping or antiphonal duets while in others, competitors antagonistically vocalize, engaging in counter-singing. Among non-primate mammals these vocalizations are considered rare and poorly understood. We provide an overview of antiphonal calling, duetting and counter-singing in non-primate mammals. Many of these coordinated vocalizations play a role in social interactions and allow mammals to convey information to other members of the social unit in visually inaccessible environments. South American Bamboo ratsDactylomysspp. are arboreal bamboo specialists found in dense bamboo thickets in Bolivia, Peru, Ecuador, Brazil and Colombia. These nocturnal rodents are rarely seen but can be easily heard because of their loud and distinctive staccato vocalizations. We provide some evidence that Bamboo rats engage in duetting, and as such they provide another case of a mammalian species, in which to investigate temporally coordinated interactive singing. We urge researchers to work toward common definitions of temporally coordinated vocalizations and to search for more mammals that utilize such vocalizations.