Vervet Research Articles

Molecular evidence of Anaplasma phagocytophilum in olive baboons and vervet monkeys in Kenya

BackgroundNonhuman primates (NHPs) play a significant role in zoonotic spill-overs, serving as either reservoirs, or amplifiers, of multiple neglected tropical diseases, including tick-borne infections. Anaplasma phagocytophilum are obligate intracellular bacteria of the family Anaplasmatacae, transmitted by Ixodid ticks and cause granulocytic anaplasmosis (formerly known as Human Granulocytic Ehrlichiosis (HGE)) in a wide range of wild and domestic mammals and humans too. The aim of this study was to determine whether Anaplasma phagocytophilum was circulating in olive baboons and vervet monkeys in Laikipia County, Kenya.ResultsSome 146 blood samples collected from olive baboons and 18 from vervet monkeys from Mpala Research Center and Ol jogi Conservancy in Laikipia County were screened for the presence of Anaplasma species using conventional Polymerase Chain Reaction (PCR), and then A. phagocytophilum was confirmed by sequencing using conventional PCR targeting 16S rRNA. This study found an overall prevalence of 18.3% for Anaplasma species. DNA sequences confirmed Anaplasma phagocytophilum in olive baboons for the first time in Kenya.ConclusionThis study provides valuable information on the endemicity of A. phagocytophilum bacteria in olive baboons in Kenya. Future research is needed to establish the prevalence and public health implications of zoonotic A. phagocytophilum isolates and the role of nonhuman primates as reservoirs in the region.

Sick and tired: sickness behaviour, polyparasitism and food stress in a gregarious mammal

Although sickness behaviour in response to non-lethal parasites has been documented in wild animals, it remains unclear how social and environmental stress might also shape an animal’s behavioural response to parasitism, nor do we know whether simultaneous infection with more than one parasite changes the way animals respond. Here, we combine physiological, environmental, behavioural and parasite measures to investigate behavioural responses to infection in wild vervet monkeys (Chlorocebus pygerythrus) living in a semi-arid region of South Africa. We quantified both activity budget and behavioural predictability to investigate the occurrence of sickness behaviour and infection with two non-lethal gastrointestinal parasite genera. Higher parasite load was linked to an increase in the time spent resting. However, the nature of the relationship with other behaviours was contingent on both the parasite genus in question and parasite species interacted, highlighting the importance of considering co-infection. Overall, food availability was the dominant predictor of behavioural change suggesting that, for monkeys living in a more extreme environment, coping with ecological stress may override the ability to modulate behaviour in response to other physiological stressors. Our findings provide insight into how animals living in harsh environments find ways to cope with parasite infection, avoidance and transmission. Sickness behaviour is a suite of behaviours that occur in response to infection that may serve as an adaptive response to cope with infection. For wild animals, the ability to express sickness behaviour will be modulated by the presence of other competing stressors. Hence, the patterns shown are likely to be more complex than under captive conditions, which is where most of our knowledge of sickness behaviour comes from. Using physiological, environmental, behavioural and parasite measures, we demonstrate that although vervet monkeys (Chlorocebus pygerythrus) living in a semi-arid region of South Africa do exhibit sickness behaviours, this is contingent on the parasite genus in question. Further, food availability was the dominant predictor of behavioural change suggesting that, for monkeys living in a more extreme environment, coping with severe ecological stress may override the ability to express sickness behaviour in an adaptive fashion.

Cortical gray matter volume and working memory in a NHP model of AD‐like neuropathology

AbstractBackgroundAge‐related neurodegeneration characteristic of late‐onset Alzheimer’s disease (LOAD) begins in middle age, well before symptoms. Therefore, translational models to identify modifiable risk factors in middle‐age are needed to understand the etiology and identify early therapeutic targets for intervention. Vervet monkeys (Chlorocebus aethiops sabaeus), like humans, have complex central nervous systems and naturally develop several risk factors for LOAD with age, including obesity, prediabetes, hypertension and decline in physical function. Furthermore, aged vervets also recapitulate many of the characteristics of early AD that are associated with reduced brain volumes, including human‐like Aβ accumulation in the brain, greater Aβ plaque burden, and reduced CSF Aβ. Thus, these NHPs are ideal models for studying healthy versus neuropathological aging.MethodUsing structural magnetic resonance imaging and cognitive assessments, we examined the relationships between age, working memory, and neuroanatomy by measuring the thicknesses and volumes of AD‐signature cortical regions of interest (“meta‐ROIs”) in 46 middle‐aged to elderly female vervets (8‐29 years of age).ResultUsing linear mixed effects models with age as a fixed effect and individual as a random effect, we found that cortical gray matter volume significantly decreased with increasing age (β=‐51.94, SE=14.37; t=‐3.61; p<0.001). The thickness of the AD‐signature meta‐ROIs was not affected by age (β<0.01, SE<0.01; t=‐0.19; p=0.85), however, the volumetric meta‐ROI tended to decline with age in older animals (β=‐6.95, SE= 4.20; t=‐1.65; p= 0.098). In the precuneus, a component region of the meta‐ROI that has been shown to be reduced in preclinical AD, volume decreased with increasing age (β=‐1.69, SE=0.72; t=‐2.36; p= 0.023). In addition to these age‐related effects, the volume of the AD‐signature meta‐ROI was positively correlated with performance on the delayed response test of working memory (R= 0.235; p=0.026).ConclusionTaken together, these findings demonstrate that cortical gray matter diminishes with age in vervet monkeys in regions relevant to AD risk, and is associated with cognitive impairment. This study provides important insights about the relationships between age, neuroanatomy, and memory in vervets, and lays the groundwork for future investigations to identify at‐risk phenotypes such that therapeutic interventions may be tested in this nonhuman primate model.

Assessment of conservation challenges in and around Gibe Sheleko National Park, southwestern Ethiopia

Most of Ethiopia’s National Parks are affected by anthropogenic factors. The objective of this study was to assess the major wildlife threatening factors of Gibe Sheleko National Park (GSNP) through semi-structured questionnaire, focus groups discussion and observation. The survey was carried out from December, 2018 to August, 2020. A total of 281 randomly selected household heads from eight Kebeles and 15 Park management staff were interviewed. The identified threats include: overgrazing, expansion of human settlement and agricultural practices, fuelwood collection, source of food (bushmeat, fishes and wild honey) collection, invasive vegetation species, human induced fire, human-wildlife conflict and source of house construction materials. The majority (71.17%) of the respondents used the Park as means of grazing land followed by sources of fuelwood (48.26%). Crop raiding is a serious problem in the study area as stated by 84.46% of the respondents. Identified crop raiders include: olive baboon, vervet monkey, warthog, bushpig, porcupine, hippopotamus and antelope species. About 78.14% of the respondents stated that guarding was the most common type of crop raiders’ protection method. The majority (55.26%) of the respondents had positive attitudes towards conservation of the Park. Significant variation was observed in the types of natural resource utilization, types of human-wildlife conflict, trends of crop damage, population status of crop raiders, methods used to protect crop raiders and their attitudes towards GSNP conservation (P < 0.05). In general, GSNP is exposed to multiple conservation challenges. Therefore, for the sustainability of the Park, cooperation among different stakeholders is essential.

Integrated omics analysis reveals sirtuin signaling is central to hepatic response to a high fructose diet

BackgroundDietary high fructose (HFr) is a known metabolic disruptor contributing to development of obesity and diabetes in Western societies. Initial molecular changes from exposure to HFr on liver metabolism may be essential to understand the perturbations leading to insulin resistance and abnormalities in lipid and carbohydrate metabolism. We studied vervet monkeys (Clorocebus aethiops sabaeus) fed a HFr (n=5) or chow diet (n=5) for 6 weeks, and obtained clinical measures of liver function, blood insulin, cholesterol and triglycerides. In addition, we performed untargeted global transcriptomics, proteomics, and metabolomics analyses on liver biopsies to determine the molecular impact of a HFr diet on coordinated pathways and networks that differed by diet.ResultsWe show that integration of omics data sets improved statistical significance for some pathways and networks, and decreased significance for others, suggesting that multiple omics datasets enhance confidence in relevant pathway and network identification. Specifically, we found that sirtuin signaling and a peroxisome proliferator activated receptor alpha (PPARA) regulatory network were significantly altered in hepatic response to HFr. Integration of metabolomics and miRNAs data further strengthened our findings.ConclusionsOur integrated analysis of three types of omics data with pathway and regulatory network analysis demonstrates the usefulness of this approach for discovery of molecular networks central to a biological response. In addition, metabolites aspartic acid and docosahexaenoic acid (DHA), protein ATG3, and genes ATG7, and HMGCS2 link sirtuin signaling and the PPARA network suggesting molecular mechanisms for altered hepatic gluconeogenesis from consumption of a HFr diet.

Scatterometry Measurements With Scattered Light Imaging Enable New Insights Into the Nerve Fiber Architecture of the Brain

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.

Hormonal correlates of male dominance rank, age, and genital colouration in vervet monkey (Chlorocebus pygerythrus)

Primates are the most colourful members of the Mammalian clade. In vervet monkeys (Chlorocebus pygerythrus), males are characterized by their red penis and blue scrotum. Such colour signals are often used in conspecific communication, and thus could be used to convey signaller condition. We quantified scrotal and penile colour characteristics using digital photographs between May-June 2016 from males in two neighboring groups along the shores of Lake Nabugabo, Uganda. We examined the relationship between fecal hormones, male dominance rank, age (adult vs. immature), and colour. Adult males were higher ranking than immatures, but there were no rank or age differences in fecal hormone levels. Glucocorticoids and androgens were positively correlated in immature, but not adult males. All scrotal characteristics were predicted by age, with adult males having more teal (i.e., less blue, more green) and more luminant scrota. Within adult males, those with higher androgens levels had more saturated blue scrotal colouration and higher-ranking males were more luminant. Penile colouration was also associated with age and rank. High-ranking males had a more saturated red penis, and adult male penile colour was more luminant and bluer than in immature males. Our findings are consistent with previous reports that scrotal colouration advertises sexual or reproductive maturity (i.e., age), but we also find that within adult males, colour also advertises dominance rank and may be mediated by androgen levels. Penile colouration also appears to signal information about male age and dominance rank but does not appear to be mediated by hormones.

Does powder averaging remove dispersion bias in diffusion MRI diameter estimates within real 3D axonal architectures?

Noninvasive estimation of axon diameter with diffusion MRI holds the potential to investigate the dynamic properties of the brain network and pathology of neurodegenerative diseases. Recent studies use powder averaging to account for complex white matter architectures, but these have not been validated for real axonal geometries from regions that contain fibre crossings. Here, we present 120−304μm long segmented axons from X-ray nano-holotomography volumes of a splenium and crossing fibre region of a vervet monkey brain. We show that the axons in the complex crossing fibre region, which contains callosal, association, and corticospinal connections, exhibit a wider diameter distribution than those of the splenium region. To accurately estimate the axon diameter in these regions, therefore, sensitivity to a wide range of diameters is required. We demonstrate how the q-value, b-value, signal-to-noise ratio and the assumed intra-axonal parallel diffusivity influence the range of measurable diameters with powder average approaches. Furthermore, we show how Gaussian distributed noise results in a wider range of measurable diameter at high b-values than Rician distributed noise, even at high signal-to-noise ratios of 100. The number of gradient directions is also shown to impose a lower bound on measurable diameter. Our results indicate that axon diameter estimation can be performed with only few b-shells, and that additional shells do not improve the accuracy of the estimate. For strong gradients available on human Connectom and preclinical scanners, Monte Carlo simulations of diffusion confirm that powder averaging techniques succeed in providing accurate estimates of axon diameter across a range of diameters, sequence parameters and diffusion times, even in complex white matter architectures. At relatively low b-values, the diameter estimate becomes sensitive to axonal microdispersion and the intra-axonal parallel diffusivity shows time dependency at both in vivo and ex vivo intrinsic diffusivities.

Fevers and the social costs of acute infection in wild vervet monkeys

Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

The Inhibition of the Degrading Enzyme Fatty Acid Amide Hydrolase Alters the Activity of the Cone System in the Vervet Monkey Retina.

Recent studies using full-field electroretinography (ffERG) that triggers a non-specific mass response generated by several retinal sources have attributed an important role for cannabinoid receptors in mediating vision in primates. Specific cone-mediated responses evoked through the photopic flicker ERG appear to be a better way to validate the assumption that endogenous cannabinoids modulate the cone pathway, since FAAH is mainly expressed in the vervet monkey cone photoreceptors. The aim of this study is two-fold: (1) to use the photopic flicker ERG to target the cone pathway specifically, and (2) use URB597 as a selective inhibitor of the endocannabinoid degrading enzyme Fatty Acid Amide Hydrolase (FAAH) to enhance the levels of fatty acid amides, particularly anandamide. We recorded ERGs under four different flicker frequencies (15, 20, 25, and 30 Hz) in light-adapted conditions after intravitreal injections of URB597. Our results show that intravitreal injections of URB597, compared to the vehicle DMSO, increased significantly ffERG amplitudes at 30 Hz, a frequency that solely recruits cone activity. However, at 15 Hz, a frequency that activates both rods and cones, no significant difference was found in the ERG response amplitude. Additionally, we found no differences in implicit times after URB597 injections compared to DMSO vehicle. These results support the role of molecules degraded by FAAH in cone-mediated vision in non-human primates.

A Meta-Analysis of Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), African green monkeys (Chlorocebus aethiops), and Ferrets (Mustela putorius furo) as Large Animal Models for COVID-19.

Animal models are at the forefront of biomedical research for studies of viral transmission, vaccines, and pathogenesis, yet the need for an ideal large animal model for COVID-19 remains. We used a meta-analysis to evaluate published data relevant to this need. Our literature survey contained 22 studies with data relevant to the incidence of common COVID-19 symptoms in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), African green monkeys (Chlorocebus aethiops), and ferrets (Mustela putorius furo). Rhesus macaques had leukocytosis on Day 1 after inoculation and pneumonia on Days 7 and 14 after inoculation, in frequencies that were similar enough to humans to reject the null hypothesis of a Fisher exact test. However, the differences in overall presentation of disease were too different from that of humans to successfully identify any of these 4 species as an ideal large animal of COVID-19. The greatest limitation to the current study is a lack of standardization in experimentation and reporting. To expand our understanding of the pathology of COVID-19 and evalu- ate vaccine immunogenicity, we must extend the unprecedented collaboration that has arisen in the study of COVID-19 to include standardization of animal-based research in an effort to find the optimal animal model.

Epigenetic clock and methylation studies in vervet monkeys

DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.

Wild female vervet monkeys change grooming patterns and partners when freed from feeding constraints

Social animals face daily challenges to fulfil feeding, resting and social needs. In vervet monkeys, Chlorocebus pygerythrus , females are the core of the social group, in which relationships are mainly established and maintained through grooming. However, social relationships are not necessarily mutual or driven by the same interests. In a complex and diverse social environment, individuals may benefit from the ability to adapt their manoeuvring to different pressures. We experimentally manipulated the activity budget of two adult females (fed subjects) per group in four wild groups to investigate activity budgets, grooming behaviour variation and the implications for possible changes in social interactions. Specifically, we provisioned food to one fed subject at a time for 2 weeks (treatment), evaluated changes in their grooming behaviour before, during and after being fed, and compared their behaviour with that of the remaining adult females in the group (nonfed subjects) over the same period. In the provisioning phase, the fed subjects decreased feeding time, but increased resting and social time. We found that fed subjects increased their grooming strength and ratio of grooming given to received and showed preferences to groom existing partners, kin and adult females. Moreover, we found no carryover effect of provisioning on grooming strength after the treatment terminated. Our results demonstrate rapid social behaviour plasticity following manipulation of ecological conditions for specific female individuals, allowing for flexible shifts in grooming patterns that hint at Machiavellian-like adjustments that may help achieve social benefits through, at least partially, restructuring their social network when experimentally released from daily feeding obligations. • Grooming is a key behaviour for primates to keep social relationships. • With an experimental approach, we compare female vervet monkeys' grooming dynamics. • The fed subjects increased their grooming given compared to grooming received. • The fed subjects preferentially groomed bonded, kin and adult female individuals. • Vervet monkeys flexibly changed their grooming during and after the treatment.

Species Composition, Diversity, and Habitat Association of Medium- and Large-Sized Mammals in Chimit-Kolla, Abay Gorge, Ethiopia

Identifying the species distribution, diversity, and habitat association provides input to launch proper conservation interventions. A survey of medium- and large-sized mammal species was conducted in Chimit-Kolla area to assess their distribution, diversity, and relative abundance in November 2019 to September 2020. Line transect sampling and focus group discussions were used for data collection. Shannon diversity index and Sorenson’s coefficient were used to compute the diversity and habitat utilization of species. The association of species among habitats was tested using the chi-squared test. In the survey, 18 species of medium- and large-sized mammals belonging to the order Artiodactyla (7 species), Carnivora (6 species), Rodentia (1 species), Primates (3 species) and Tubulidentata (1 species) were recorded. The association of mammalian species among the three habitats was not significant ( p &gt; 0.05 ). However, the abundance of mammal species was significantly associated with forest habitats ( p &lt; 0.05 ). There was a significant variation in abundance of medium- and large-sized mammal species observed in the dry season (157, 57.5%) as compared to the wet season (116, 42.5%) (χ2 = 6.17, df = 1, and p = 0.013 ). The most abundant species was olive baboon (Papio anubis), followed by grivet monkey (Chlorocebus aethiops) and crested porcupine (Hystrix cristata). While leopard (Panthera pardus), white-tailed mongoose (Ichneumia albicauda), and aardvark (Orycteropus afer) were the rarest mammalian species recorded. Forest habitat has the highest species diversity (H’ = 2.276) than riverine vegetation and wooded grassland. Mammal species showed a considerable similarity among habitats, and the highest similarity was recorded between forest and wooded grassland (S = 0.8). The study area relatively has considerable numbers of medium- and large-sized mammal species, and urgent conservation action is required to reduce the emerging threats (hunting, charcoal production, agriculture, and investment expansion) and ensure survival of mammal species.

Keep calm and carry on: reactive indifference to predator encounters by a gregarious prey species

Strategies that mitigate predation, whether proactive or reactive, can nevertheless impose significant ‘nonconsumptive’ costs on prey species. Here we used data from two wild vervet monkey, Chlorocebus pygerythru,s groups to assess whether the detection of predators affected their subsequent behaviour to the detriment of their short-term foraging effort. Encounters with the three predator classes present at our study site were frequent and there was evidence that animals were more likely to shift to predator-focused vigilance, which was modulated by alarm call intensity, but not predator type, in the hour following detection. Nevertheless, and against expectation, there was no detectable shift in overall levels of vigilance, which remained low, interindividual distances, travel bearing and, consequently, effort put into foraging. We consider this surprising imperturbability by our study groups in the context of population group size, as our groups are large and have correspondingly lower levels of individual vigilance, as well as in terms of the constraints imposed by small, overlapping territories and frequent predator encounters. Finally, we advocate for increased consideration of the responses of the predators themselves to detection by their prey. • We observed vervet monkeys to assess whether predators affect vigilance and foraging. • Vervets were as likely to forage after predator encounters as they were before. • While female vervets were more vigilant, both sexes were generally unperturbed. • Predator type did not affect the likelihood of vigilance. • We explain this surprising indifference to predators in terms of large group size.

Epigenetic clock and methylation studies in the rhesus macaque

Methylation levels at specific CpG positions in the genome have been used to develop accurate estimators of chronological age in humans, mice, and other species. Although epigenetic clocks are generally species-specific, the principles underpinning them appear to be conserved at least across the mammalian class. This is exemplified by the successful development of epigenetic clocks for mice and several other mammalian species. Here, we describe epigenetic clocks for the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate in biological research. Using a custom methylation array (HorvathMammalMethylChip40), we profiled n = 281 tissue samples (blood, skin, adipose, kidney, liver, lung, muscle, and cerebral cortex). From these data, we generated five epigenetic clocks for macaques. These clocks differ with regard to applicability to different tissue types (pan-tissue, blood, skin), species (macaque only or both humans and macaques), and measure of age (chronological age versus relative age). Additionally, the age-based human-macaque clock exhibits a high age correlation (R = 0.89) with the vervet monkey (Chlorocebus sabaeus), another Old World species. Four CpGs within the KLF14 promoter were consistently altered with age in four tissues (adipose, blood, cerebral cortex, skin). Future studies will be needed to evaluate whether these epigenetic clocks predict age-related conditions in the rhesus macaque.

DNA methylation age analysis of rapamycin in common marmosets

Human DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

Communication before communicative intentions

AbstractThis paper explores the significance of intelligent social behavior among non‐human animals for philosophical theories of communication. Using the alarm call system of vervet monkeys as a case study, I argue that interpersonal communication (or what I call “minded communication”) can and does take place in the absence of the production and recognition of communicative intentions. More generally, I argue that evolutionary theory provides good reasons for maintaining that minded communication is both temporally and explanatorily prior to the use of communicative intentions. After developing these negative points about the place of communicative intentions in detail, I provide a novel alternative account according to which minded communication is characterized in terms of patterns of action and response that function to coordinate the representational mental states of agents. I show that an account which centers on patterns of representational coordination of this sort is well suited to capture the theoretical roles associated with minded communication and that it does so in a way that provides a good fit with comparative facts about the presence of minded communication among non‐human animals.

Dietary and Pharmacologic Manipulations of Host Lipids and Their Interaction With the Gut Microbiome in Non-human Primates.

The gut microbiome influences nutrient processing as well as host physiology. Plasma lipid levels have been associated with the microbiome, although the underlying mechanisms are largely unknown, and the effects of dietary lipids on the gut microbiome in humans are not well-studied. We used a compilation of four studies utilizing non-human primates (Chlorocebus aethiops and Macaca fascicularis) with treatments that manipulated plasma lipid levels using dietary and pharmacological techniques, and characterized the microbiome using 16S rDNA. High-fat diets significantly reduced alpha diversity (Shannon) and the Firmicutes/Bacteroidetes ratio compared to chow diets, even when the diets had different compositions and were applied in different orders. When analyzed for differential abundance using DESeq2, Bulleidia, Clostridium, Ruminococcus, Eubacterium, Coprocacillus, Lachnospira, Blautia, Coprococcus, and Oscillospira were greater in both chow diets while Succinivibrio, Collinsella, Streptococcus, and Lactococcus were greater in both high-fat diets (oleic blend or lard fat source). Dietary cholesterol levels did not affect the microbiome and neither did alterations of plasma lipid levels through treatments of miR-33 antisense oligonucleotide (anti-miR-33), Niemann–Pick C1-Like 1 (NPC1L1) antisense oligonucleotide (ASO), and inducible degrader of LDLR (IDOL) ASO. However, a liver X receptor (LXR) agonist shifted the microbiome and decreased bile acid levels. Fifteen genera increased with the LXR agonist, while seven genera decreased. Pseudomonas increased on the LXR agonist and was negatively correlated to deoxycholic acid, cholic acid, and total bile acids while Ruminococcus was positively correlated with taurolithocholic acid and taurodeoxycholic acid. Seven of the nine bile acids identified in the feces significantly decreased due to the LXR agonist, and total bile acids (nmol/g) was reduced by 62%. These results indicate that plasma lipid levels have, at most, a modest effect on the microbiome, whereas bile acids, derived in part from plasma lipids, are likely responsible for the indirect relationship between lipid levels and the microbiome.

Isoform-specific dysregulation of AMP-activated protein kinase signaling in a non-human primate model of Alzheimer's disease

AMP-activated protein kinase (AMPK) is a molecular sensor that is critical for the maintenance of cellular energy homeostasis, disruption of which has been indicated in multiple neurodegenerative diseases including Alzheimer's disease (AD). Mammalian AMPK is a heterotrimeric complex and its enzymatic α subunit exists in two isoforms: AMPKα1 and AMPKα2. Here we took advantage of a recently characterized non-human primate (NHP) model with sporadic AD-like neuropathology to explore potential relationships between AMPK signaling and AD-like neuropathology. Subjects were nine female vervet monkeys aged 19.5 to 23.4 years old. Subjects were classified into three groups, control lacking AD pathology (n = 3), moderate AD pathology (n = 3), and more severe AD Pathology (n = 3). We found increased activity (assessed by phosphorylation) of AMPKα2 in hippocampi of NHP with AD-like neuropathology, compared to the subjects without AD pathology, with no alterations of AMPKα1 activity. Across all subjects, CSF Abeta42 was inversely associated with cerebral amyloid plaque density. Further, Aβ plaque burden is correlated with levels of either soluble or insoluble brain Aβ measurement. Unbiased mass spectrometry based proteomics studies combined with bioinformatics analysis revealed that many of the dysregulated proteins characteristic of AD neuropathology are associated with AMPK signaling. Our findings on the AMPK molecular signaling cascades provide further support for use of the NHP model to investigate new therapeutic strategies and development of novel biomarkers for Alzheimer's disease.