Male Baboons Research Articles

Abstract 4117594: Fetal Synthetic Glucocorticoid (sGC) Exposure Results in Later Life Cardiac Dysfunction and Ventricular Remodeling in Male Baboon Offspring

The “theory of developmental origins of health and disease” posits that stress in critical developmental periods will program life-course health and may affect cardiovascular (CV) health. Mothers at risk for premature delivery receive synthetic glucocorticoids (sGC) to enhance fetal lung maturation and manage fetal respiratory distress, but sGC exposure is linked to long-term CV dysfunction in offspring. Four groups of male baboons were studied: sGC exposed in utero at middle age (sGC-MA, 13.8±0.2Y), older sGC exposed in utero (sGC-O, 17.1±0.4Y), middle age unexposed (CTR-MA, 13.5±0.6Y), and older, unexposed baboons (CTR-O, 17.4±0.4Y). Gated, breath-hold, cine cardiac magnetic resonance imaging was performed at 3 Tesla (Siemens TIM Trio) to assess left ventricular (LV) function and myocardial strain, analyzed using cvi42® software. Mitochondrial electron transport chain (ETC) complex activity was analyzed using LV tissue from sGC-O and CTR-O euthanized baboons. Protein quantification was used to measure mitochondrial function and RNA-seq assessed differential gene expression and gene ontology (GO) enrichment. Unpaired t-tests were used. Data are reported as mean ± SD. Stroke volume and ejection fraction were similar in the elderly groups (4 sGC-O, 8 CTR-O). However, higher end-systolic and end-diastolic sphericity indexes (SI) and shorter LV axis lengths indicated remodeling. Also, global longitudinal and radial strains were reduced (both p<0.04) in sGC-O vs. CTR-O. Reduced LV cardiac output (p=0.005) was found in 5 sGC-MA animals vs 4 sGC-O animals, but not in 5 CTR-MA vs 8 CTR-O. In sGC-MA vs sGC-O, but not CTR-MA vs CTR-O, significant increases in SI (p=0.001), radial strain (p=0.02), and longitudinal (p=0.03) strain were found, but LV axis length (p=0.03) was reduced. LV mitochondrial analysis in 4 sGC-O vs 4 CTR-O myocardial samples revealed 33.5% less ETC activity (p=0.002) and 19.8% less complex I expression (p=0.048) in sGC. LV RNA-seq identified 63 upregulated and 20 downregulated genes in the sGC-O samples. GO pathway enrichment included changes in heart contraction, wounding responses, and leukocyte regulation pathways. These findings indicate that fetal sGC exposure developmentally programs offspring with LV remodeling and long-term cardiac and gene expression changes in male baboons, the closest available experimental nonhuman primate species to man. Future studies on females will probe sexual dimorphism in developmental programming.

Oxytocin decreases alcohol self-administration in male baboons

The neurohormone oxytocin (OT) has been proposed as a treatment for alcohol and nicotine use disorders. The aim of the present study was to examine whether intravenous (IV) OT decreases alcohol oral self-administration and consumption in nonhuman primates under a 6-h alcohol access procedure as well as alcohol and nicotine (IV) self-administration under 6-h concurrent access conditions. The subjects were five male baboons (Papio anubis) that self-administered oral alcohol (4% w/v) during 6-h sessions under a fixed ratio 3 (FR3) schedule per drink. Baseline levels of alcohol self-administration were established and then OT treatment was initiated. A single dose of OT (20, 40, 80, 120 IU, IV) or its vehicle (saline) was administered before and again in the middle of the 6-h drinking session for 5 consecutive days (total oxytocin dose of 40, 80, 160, 240 IU/day). After each 5-day treatment, baseline levels of alcohol self-administration were reestablished before the next 5-day OT treatment. In addition, the effect of OT on concurrent alcohol and IV nicotine self-administration was explored in 3 of the baboons where alcohol and nicotine were concurrently available during the 6-hr session each under an FR3 schedule for each drug. Establishment of baseline self-administration and 5-day OT treatments were completed as in the alcohol only study. There was a significant overall reduction in alcohol consumption with OT compared to placebo. On post-hoc analysis, after correcting for multiple comparisons, the 40 and 80 IU doses of OT significantly reduced alcohol consumption compared with vehicle, and consumption did not vary significantly within each 5-day treatment period. OT, qualitatively, also reduced the coadministration of both alcohol and nicotine in each baboon for at least one of the OT doses administered. These results underscore the therapeutic potential of oxytocin as a treatment of alcohol use disorder and possibly, co-use of nicotine.

Variation in Craniodental Pathologies Among Cercopithecoid Primates.

Pathologies of the skull and teeth are well documented for many human populations, but there are fewer studies of other primates. We contrast lesion prevalence and patterning among cercopithecoid primates and map variation onto socioecological variables. We compare craniodental lesions in six species: Nasalis larvatus (n = 54), Colobus polykomos (n = 64), Cercopithecus mitis (n = 65), Macaca fascicularis (n = 109), Theropithecus gelada (n = 13), and Papio anubis (n = 76). One of us (C.A.K.) evaluated each adult skull for multiple lesion types using standard criteria. We also tested for a relationship between lesion prevalence and cranial suture fusion (age proxy). We used nonparametric tests for sex and species differences as well as pathology co-occurrence in SPSS. Socioecological data come from previous studies. Sex differences in lesion prevalence were only detected in P. anubis. Within taxa, some lesion types co-occurred. In Macaca, the presence of caries was associated with several other lesion types. Pulp cavity exposure co-occurred with TMJ osteoarthritis in multiple taxa. Among taxa, male P. anubis had higher lesion prevalences, particularly related to the anterior dentition and facial trauma. Because we did not detect a relationship between suture fusion and lesion prevalence, we propose that craniodental lesions may also be influenced by socioecological variables such as group composition and ratio of fruit to leaves in the diet. Our findings suggest that pain from pulp cavity exposure and related dental infections may alter chewing biomechanics and contribute to onset of TMJ osteoarthritis in nonhuman primates, as seen in humans. Further, we suggest that higher lesion prevalence in male baboons is likely related to male-male competition. Skeletal lesion analysis provides useful insight into primate socioecology, particularly for rare or difficult-to-observe phenomena, and provides additional biological context for our own species.

A radioligand for in vitro autoradiography of CSF1R in post-mortem CNS tissues

BackgroundReactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer’s dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R. We report the radiosynthesis of both [3H]1 and [11C]1. The PET imaging properties of [11C]1 in mice and baboon were investigated. [3H]1 was studied in Bmax measurement in post-mortem autoradiography in the frontal cortex, inferior parietal cortex and hippocampus from donors diagnosed with AD and age-matched controls. In vitro binding affinity of 1 was measured commercially. Nor-methyl-1 precursor was radiolabeled with [11C]iodomethane or [3H]iodomethane to produce [11C]1 and [3H]1, respectively. Ex vivo brain biodistribution of [11C]1 was compared in normal mice versus lipopolysaccharide-administered (LPS) murine model of neuroinflammation. Dynamic PET imaging was performed in a healthy male Papio anubis baboon. Post-mortem autoradiography with [3H]1 was performed in frozen sections using a standard saturation binding technique.ResultsCompound 1 exhibits a high in vitro CSF1R binding affinity (0.59 nM). [11C]1 was synthesized with high yield. [3H]1 was synthesized similarly (commercially). Biodistribution of [11C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [11C]1 was ~ 50% specific for CSF1R. PET/CT [11C]1 study in baboon revealed low brain uptake (0.36 SUV) of [11C]1. Autoradiography with [3H]1 gave significantly elevated Bmax values in AD frontal cortex versus control (47.78 ± 26.80 fmol/mg vs. 12.80 ± 5.30 fmol/mg, respectively, P = 0.023) and elevated, but not significantly different binding in AD hippocampus grey matter and inferior parietal cortex (IPC) white matter.ConclusionsCompound 1 exhibits a high in vitro CSF1R binding affinity. [11C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood–brain barrier in baboon PET. [3H]1 specifically labels CSF1R in post-mortem human brain. The binding of [3H]1 is significantly higher in the post-mortem frontal cortex of AD versus control subjects.

Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons.

Biological resilience, broadly defined as the ability to recover from an acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences are likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue, and subject level. To address this question, we established primary cells from aged male and female baboons between 13.3 and 17.8years spanning across different tissues, tissue regions, and cell types including (1) fibroblasts from skin and from the heart separated into the left ventricle (LV), right ventricle (RV), left atrium (LA), and right atrium (RA); (2) astrocytes from the prefrontal cortex and hippocampus; and (3) hepatocytes. Primary cells were characterized by their cell surface markers and their cellular respiration was assessed with Seahorse XFe96. Cellular resilience was assessed by modifying a live-cell imaging approach; we previously reported that monitors proliferation of dividing cells following response and recovery to oxidative (50µM-H2O2), metabolic (1mM-glucose), and proteostasis (0.1µM-thapsigargin) stress. We noted significant differences even among similar cell types that are dependent on tissue source and the diversity in cellular response is stressor-specific. For example, astrocytes had a higher oxygen consumption rate and exhibited greater resilience to oxidative stress (OS) than both fibroblasts and hepatocytes. RV and RA fibroblasts were less resilient to OS compared with LV and LA, respectively. Skin fibroblasts were less impacted by proteostasis stress compared to astrocytes and cardiac fibroblasts. Future studies will test the functional relationship of these outcomes to the age and developmental status of donors as potential predictive markers.

Estimating individual exposure to predation risk in group-living baboons, Papio anubis.

In environments with multiple predators, vulnerabilities associated with the spatial positions of group-living prey are non-uniform and depend on the hunting styles of the predators. Theoretically, coursing predators follow their prey over long distances and attack open areas, exposing individuals at the edge of the group to predation risk more than those at the center (marginal predation). In contrast, ambush predators lurk unnoticed by their prey and appear randomly anywhere in the group; therefore, isolated individuals in the group would be more vulnerable to predators. These positions of vulnerability to predation are expected to be taken by larger-bodied males. Moreover, dominant males presumably occupy the center of the safe group. However, identifying individuals at higher predation risk requires both simultaneous recording of predator location and direct observation of predation events; empirical observations leave ambiguity as to who is at risk. Instead, several theoretical methods (predation risk proxies) have been proposed to assess predation risk: (1) the size of the individual 'unlimited domain of danger' based on Voronoi tessellation, (2) the size of the 'limited domain of danger' based on predator detection distance, (3) peripheral/center position in the group (minimum convex polygon), (4) the number and direction of others in the vicinity (surroundedness), and (5) dyadic distances. We explored the age-sex distribution of individuals in at-risk positions within a wild baboon group facing predation risk from leopards, lions, and hyenas, using Global Positioning System collars. Our analysis of the location data from 26 baboons revealed that adult males were consistently isolated at the edge of the group in all predation risk proxies. Empirical evidence from previous studies indicates that adult male baboons are the most frequently preyed upon, and our results highlights the importance of spatial positioning in this.

Osteology of the Hamadryas Baboon (Papio hamadryas).

Besides living as a free-ranging primate in the horn of Africa and the Arabian Peninsula, the hamadryas baboon has an important place in zoos and can be found in biomedical research centers worldwide. To be valuable as a non-human primate laboratory model for man, its anatomy should be portrayed in detail, allowing for the correct interpretation and translation of obtained research results. Reviewing the literature on the use of the baboon in biomedical research revealed that very limited anatomical works on this species are available. Anatomical atlases are incomplete, use archaic nomenclature and fail to provide high-definition color photographs. Therefore, the skeletons of two male hamadryas baboons were prepared by manually removing as much soft tissues as possible followed by maceration in warm water to which enzyme-containing washing powder was added. The bones were bleached with hydrogen peroxide and degreased by means of methylene chloride. Photographs of the various bones were taken, and the anatomical structures were identified using the latest version of the Nomina Anatomica Veterinaria. As such, the present article shows 31 annotated multipanel figures. The skeleton of the hamadryas baboon generally parallels the human skeleton, but some remarkable differences have been noticed. If these are taken into consideration when evaluating the results of experiments using the hamadryas baboon, justified conclusions can be drawn.

The effects of early rearing experiences on mutual eye gaze among captive olive baboons (Papio anubis).

Among human and nonhuman primates, mutual eye gaze (MEG) and gaze following are believed to be important for social cognition and communicative signaling. The goals of this study were to examine how early rearing experiences contribute to individual variation in MEG and to examine the potential role of genetic factors underlying this variation. Subjects included 93 female and 23 male baboons (Papio anubis) ranging from 3 to 20 years of age. Within the sample, there were 55 mother-reared (MR) and 61 nursery-reared (NR) baboons. MEG was assessed in four 60-s test sessions. For each session, the duration, frequency, and bout length were recorded. Mean values were then calculated for each individual from the four sessions. A multivariate analysis of covariance revealed an overall significant main effect for rearing. Subsequent univariate analyses revealed significant rearing effects on mean bout length, but not mean duration or meanfrequency, with MR baboons having longer bout lengths compared to NR baboons. Furthermore, mean bout length was found to be significantly heritable. These results indicate that rearing experiences, and to a small extent, genetic factors, affect patternsof mutual eye gaze - in particular, bout length. These results differ from previous findings in MR and NR chimpanzees, further suggesting that rearing may impact MEG in a species-specific manner that reflects the function of gaze in different primate species.

Xenografts Show Signs of Concentric Hypertrophy and Dynamic Left Ventricular Outflow Tract Obstruction After Orthotopic Pig-to-baboon Heart Transplantation.

Orthotopic cardiac xenotransplantation has seen substantial advancement in the last years and the initiation of a clinical pilot study is close. However, donor organ overgrowth has been a major hurdle for preclinical experiments, resulting in loss of function and the decease of the recipient. A better understanding of the pathogenesis of organ overgrowth after xenotransplantation is necessary before clinical application. Hearts from genetically modified ( GGTA1-KO , hCD46/hTBM transgenic) juvenile pigs were orthotopically transplanted into male baboons. Group I (control, n = 3) received immunosuppression based on costimulation blockade, group II (growth inhibition, n = 9) was additionally treated with mechanistic target of rapamycin inhibitor, antihypertensive medication, and fast corticoid tapering. Thyroid hormones and insulin-like growth factor 1 were measured before transplantation and before euthanasia, left ventricular (LV) growth was assessed by echocardiography, and hemodynamic data were recorded via a wireless implant. Insulin-like growth factor 1 was higher in baboons than in donor piglets but dropped to porcine levels at the end of the experiments in group I. LV mass increase was 10-fold faster in group I than in group II. This increase was caused by nonphysiological LV wall enlargement. Additionally, pressure gradients between LV and the ascending aorta developed, and signs of dynamic left ventricular outflow tract (LVOT) obstruction appeared. After orthotopic xenotransplantation in baboon recipients, untreated porcine hearts showed rapidly progressing concentric hypertrophy with dynamic LVOT obstruction, mimicking hypertrophic obstructive cardiomyopathy in humans. Antihypertensive and antiproliferative drugs reduced growth rate and inhibited LVOT obstruction, thereby preventing loss of function.

Analysis of the Ability to Skill Formation and Stability of the Formed Skill in Mature Male Rhesus Monkeys (Macaca mulatta) and Hamadryas Baboons (Papio hamadryas).

A comparative study of the ability to form a skill, the dynamics of its formation, and repeatability in sexually mature male rhesus monkeys (Macaca mulatta) and hamadryas baboons (Papio hamadryas) was carried out. It was found that male hamadryas baboons of the study group demonstrate higher learning ability, training level, and repeatability of the formed skill compared to the studied male rhesus monkeys. At the same time, animals of both species demonstrated similar dynamics of skill formation.

Tradeoffs between mating effort and parenting effort in a polygynandrous mammal

Reproductive strategies are defined by expenditures of time and energy devoted to mating effort, which increases mating opportunities, and parenting effort, which enhances the survival of offspring. We examine tradeoffs between mating effort and parenting effort in male olive baboons, Papio anubis, a species in which males compete for mating opportunities, but also form ties to lactating females (primary associations) that represent a form of parenting effort. Males that are involved in more primary associations invest less in mating effort than males who are involved in fewer primary associations. Males that are involved in more primary associations play a smaller role in establishing proximity to their primary associates than other males, suggesting that males operate under temporal constraints. There is also some evidence that involvement in primary associations negatively affects paternity success. Taken together, the data suggest that males face tradeoffs between mating effort and parenting effort.

Male Guinea baboons may be oblivious to associated females' whereabouts

In group-living species, evolution puts a premium on the ability of individuals to track the state, whereabouts and interactions of others. The value of social information might vary with the degree of competition among individuals, however. We investigated male monitoring of female location in wild Guinea baboons, Papio papio. Guinea baboons live in socially tolerant multilevel societies with one-male units comprising one to six females and young at the core. Using field playback experiments, we first tested whether male Guinea baboons responded more strongly to playbacks of associated versus nonassociated females, which was the case. In the second and core experiment, we tested whether males keep track of the whereabouts of associated females by playing back unit females' calls from locations that were either consistent or inconsistent with the actual position of the female. Contrary to predictions, males responded equally strongly in both conditions. While males seem to recognize unit females by voice, they might lack the attention or motivation to track their movement patterns. These results reinforce the view that the value of social information may vary substantially with the distribution of power in a society. While highly competitive regimes necessitate high attention to deviations from expected patterns, egalitarian societies allow for a certain degree of obliviousness.

Oral Cannabidiol does not alter Alcohol Seeking and Self‐Administration in Baboons

BackgroundThe cannabinoid cannabidiol (CBD) is currently under investigation as a pharmacotherapy for alcohol use disorder. The aim of the present study was to examine whether acute and chronic treatment with pure CBD would decrease alcohol seeking and consumption behaviors or alter drinking patterns in male baboons with extensive histories of daily alcohol intake (1 g/kg/day). MethodsSeven male baboons self-administered oral alcohol (4% w/v) in a validated chained schedule of reinforcement (CSR) procedure that modeled periods of anticipation, seeking, and consumption. In Experiment 1, CBD (5–40 mg/kg) or vehicle (peanut oil, USP) was administered orally 15- or 90-minutes prior to the start of the session. In Experiment 2, oral doses of CBD (10–40 mg/kg) or vehicle were administered for 5 consecutive days during ongoing alcohol access under the CSR. In addition, behavioral observations were conducted to assess potential drug side effects (e.g., sedation, motor incoordination) following chronic CBD treatment immediately after the session and 24-hours after drug administration. ResultsAcross both experiments, baboons self-administered an average of 1 g/kg/day of alcohol under baseline conditions. Administration of acute or chronic CBD (150–1200 mg total CBD dose/day) that encompassed the purported therapeutic dose range did not significantly reduce alcohol seeking, self-administration or intake (g/kg). Drinking patterns (i.e., number of drinks/bouts, bout duration, nor interdrink interval) also were not altered. There were no observable behavioral disruptions following CBD treatment. ConclusionsIn sum, the current data do not support use of pure CBD as an effective pharmacotherapy to reduce ongoing excessive drinking.

SEX DIFFERENCES IN MITOCHONDRIAL RESILIENCE: EVIDENCE FROM BABOON HEPATOCYTES

Abstract Events that occur in utero set the trajectory for later-life diseases and longevity. Compelling data exist for interactions between developmental programming and aging, but the underlying mechanisms are not clearly defined. Fetal exposure to glucocorticoids (GC) is associated with alteration in hepatic enzymes and metabolic function in later life. We previously reported increased hepatic lipid accumulation and obese phenotype in middle-age male baboons exposed to GC as fetuses. The mitochondria play significant roles in cellular processes including stress responses and possibly a nexus between developmental programming and aging. The present study investigated the long-term effects of in utero GC exposure on mitochondrial bioenergetics using hepatocytes derived from aging baboons (16–18 years, average lifespan 21 years). Mitochondrial bioenergetics of both left and right lobe liver hepatocytes were examined as well as potential sex differences in mitochondrial function. Cell viability following isolation was similar among sexes and liver lobes but hepatocytes from males were highly energetic compared to females. Significant bioenergetic differences were observed in hepatocytes isolated from female baboons’ left and right liver lobes, with higher basal, maximal, and ATP-linked respiration in left lobe hepatocytes compared to the right lobe. These lobe-specific bioenergetic differences were absent in males. Interestingly, H2O2-induced oxidative stress significantly modified male baboon hepatocyte bioenergetics but females were unaffected, suggesting mitochondrial resilience in females compared to males. These data demonstrate that early life exposure to GC elicits a sex-specific effect on mitochondrial function. These mitochondrial differences might drive differences in cell senescence between males and females.

CLARIFYING THE ROLE OF RESILIENCE IN NONHUMAN PRIMATE AGING USING A BABOON CELL MODEL

Abstract Aging is associated with defects in homeostatic maintenance. Delineating the dynamics of the homeostatic network is challenging in vivo and often limited by endpoint measurements. However, we have developed carefully controlled translatable cellular models to bridge some of these challenges using primary cells obtained from male and female baboons across the life course (4 to 21 years). We recently published findings showing that donor age corresponds to loss of cellular resilience to oxidative stress in males but not in females. Responses to thapsigargin-induced endoplasmic reticulum (ER) stress were also age and sex dependent, though with different pattern than that of oxidative challenge. Young females alone were vulnerable to ER stress, while young males and old females were not affected. These data highlight that primary cells retain donor characteristics regarding molecular mechanisms associated with aging including those dependent on sex. To further investigate these mechanisms, we investigated whether the proteostatic machinery contributes to cellular resilience outcome following ER stress. In female donors, we find significant decrease in 20 S proteasome activity and expression of its catalytic subunit (PSMB 8) in female-derived fibroblasts under basal or ER stress conditions when compared to males. ER oxidoreductin 1 (ERO1) as well as autophagy marker, LC3-II/I ratio, were significantly higher in young females compared to young males during ER stress. These data highlight the propagation of sexual dimorphisms in cellular resilience at the molecular level and suggest that sex differences in maintenance of proteostasis contributes to the vulnerability of young females to ER stress.

Abstract P1017: Tissue Engineered Human Acellular Blood Vessels For Coronary Artery Bypass Grafting

Objective: Conduit for coronary artery bypass grafting (CABG) can be limited due to poor quality or prior removal of saphenous veins. A human acellular vessel (HAV) bioengineered from vascular cells and then decellularized for implantation may provide a readily available, off-the-shelf conduit for CABG. Here we evaluate the use of small diameter HAV for CABG in a non-human primate model. Methods: Adult male baboons (n=7; 26.8 - 37.0 kg) were imaged by left heart catheterization and computed tomography angiography. CABG was performed using a 3.5 mm diameter HAV to the left anterior descending (LAD) or right coronary artery (RCA) via sternotomy with cardiopulmonary bypass. The proximal coronary artery was ligated to prevent competitive flow and graft transit time flowmetry (TTFM) was assessed after implant. Angiography at 2 weeks, 1, 3, and 6 months evaluated graft patency and heart function. HAVs explanted at 6 months were assessed by immunohistochemistry for host cellular response and remodeling. Results and Conclusion: Baboons underwent CABG using a 3.5 mm HAV from the ascending aorta to the LAD (n=2) or RCA (n=5). The diminutive LAD led to early graft loss due to size mismatch and poor runoff. HAV bypass to the dominant RCA (TTFM: 22 ± 7.7 mL/min) resulted in sustained graft patency for up to 6 months post-implantation. HAV explant histology revealed infiltration of multiple host cell populations with formation of a neoadventitial layer and evidence of luminal endothelization. HAV conduits retained structural integrity with no evidence of mechanical failure throughout the study. These results demonstrate that tissue-engineered HAVs may provide an off-the-shelf conduit for CABG.

Hepatic transcript signatures predict atherosclerotic lesion burden prior to a 2-year high cholesterol, high fat diet challenge.

The purpose of this study was to identify molecular mechanisms by which the liver influences total lesion burden in a nonhuman primate model (NHP) of cardiovascular disease with acute and chronic feeding of a high cholesterol, high fat (HCHF) diet. Baboons (47 females, 64 males) were fed a HCHF diet for 2 years (y); liver biopsies were collected at baseline, 7 weeks (w) and 2y, and lesions were quantified in aortic arch, descending aorta, and common iliac at 2y. Unbiased weighted gene co-expression network analysis (WGCNA) revealed several modules of hepatic genes correlated with lesions at different time points of dietary challenge. Pathway and network analyses were performed to study the roles of hepatic module genes. More significant pathways were observed in males than females. In males, we found modules enriched for genes in oxidative phosphorylation at baseline, opioid signaling at 7w, and EIF2 signaling and HNF1A and HNF4A networks at baseline and 2y. One module enriched for fatty acid β oxidation pathway genes was found in males and females at 2y. To our knowledge, this is the first study of a large NHP cohort to identify hepatic genes that correlate with lesion burden. Correlations of baseline and 7w module genes with lesions at 2y were observed in males but not in females. Pathway analyses of baseline and 7w module genes indicate EIF2 signaling, oxidative phosphorylation, and μ-opioid signaling are possible mechanisms that predict lesion formation induced by HCHF diet consumption in males. Our findings of coordinated hepatic transcriptional response in male baboons but not female baboons indicate underlying molecular mechanisms differ between female and male primate atherosclerosis.

Molecular Approaches for the Validation of the Baboon as a Nonhuman Primate Model for the Study of Zika Virus Infection.

Nonhuman primates (NHP) are particularly important for modeling infections with viruses that do not naturally replicate in rodent cells. Zika virus (ZIKV) has been responsible for sporadic epidemics, but in 2015 a disseminated outbreak of ZIKV resulted in the World Health Organization declaring it a global health emergency. Since the advent of this last epidemic, several NHP species, including the baboon, have been utilized for modeling and understanding the complications of ZIKV infection in humans; several health issues related to the outcome of infection have not been resolved yet and require further investigation. This study was designed to validate, in baboons, the molecular signatures that have previously been identified in ZIKV-infected humans and macaque models. We performed a comprehensive molecular analysis of baboons during acute ZIKV infection, including flow cytometry, cytokine, immunological, and transcriptomic analyses. We show here that, similar to most human cases, ZIKV infection of male baboons tends to be subclinical, but is associated with a rapid and transient antiviral interferon-based response signature that induces a detectable humoral and cell-mediated immune response. This immunity against the virus protects animals from challenge with a divergent ZIKV strain, as evidenced by undetectable viremia but clear anamnestic responses. These results provide additional support for the use of baboons as an alternative animal model to macaques and validate omic techniques that could help identify the molecular basis of complications associated with ZIKV infections in humans.

Immigrant males’ knowledge influences baboon troop movements to reduce home range overlap and mating competition

Abstract Mechanistic models suggest that individuals’ memories could shape home range patterns and dynamics, and how neighbors share space. In social species, such dynamics of home range overlap may be affected by the pre-dispersal memories of immigrants. We tested this “immigrant knowledge hypothesis” in a wild population of chacma baboons (Papio ursinus). We predicted that overlap dynamics with a given neighboring troop’s home range should reflect males’ adaptive interests in overlap when the alpha male had immigrated from this neighboring troop but less so when the alpha male originated from elsewhere. We used data collected between 2005 and 2013 on two neighboring troops in Namibia, comprising GPS records of daily ranges, male natal origins, daily females’ reproductive status, and a satellite index of vegetation growth. We found support for our prediction in line with male reproductive strategies but not in line with foraging conditions. In periods with a higher relative number of fertile females over adult males in the focal troop, male baboons would benefit from reducing overlap with their neighbors to mitigate the costs of between-troop mating competition. This was indeed observed but only when the alpha male of the focal troop was an immigrant from that neighboring troop, and not with alpha males of other origins, presumably due to their different knowledge of the neighboring troop. Our findings highlight the role of reproductive competition in the range dynamics of social groups, and suggest that spatial segregation between groups could increase through the combination of dispersal and memory.

Study the Differences between the Parameters of Learning and Exploratory Activities in Adult Male Rhesus Monkeys (Macaca mulatta) and Baboon Hamadryas (Papio hamadryas).

We studied exploratory activity and learning ability in sexually mature male rhesus monkeys (Macaca mulatta) and hamadryas baboons (Papio hamadryas). The interspecies differences were analyzed by the following parameters: the level of exploratory activity, diversity of exploratory activity, concentration on the object, learning ability, training levels, and dynamics of learning. The studied group of hamadryas baboons showed higher levels of exploratory activity and learning ability than the group of rhesus monkeys.