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ELife May 2023Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these...
Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these relationships is essential to learn how ecology scales up to affect microbiome assembly, dynamics, and host health. However, whether bacterial relationships are generalizable across hosts or personalized to individual hosts is debated. Here, we apply a robust, multinomial logistic-normal modeling framework to extensive time series data (5534 samples from 56 baboon hosts over 13 years) to infer thousands of correlations in bacterial abundance in individual baboons and test the degree to which bacterial abundance correlations are 'universal'. We also compare these patterns to two human data sets. We find that, most bacterial correlations are weak, negative, and universal across hosts, such that shared correlation patterns dominate over host-specific correlations by almost twofold. Further, taxon pairs that had inconsistent correlation signs (either positive or negative) in different hosts always had weak correlations within hosts. From the host perspective, host pairs with the most similar bacterial correlation patterns also had similar microbiome taxonomic compositions and tended to be genetic relatives. Compared to humans, universality in baboons was similar to that in human infants, and stronger than one data set from human adults. Bacterial families that showed universal correlations in human infants were often universal in baboons. Together, our work contributes new tools for analyzing the universality of bacterial associations across hosts, with implications for microbiome personalization, community assembly, and stability, and for designing microbiome interventions to improve host health.
Topics: Animals; Humans; Gastrointestinal Microbiome; Papio; Microbiota; Bacteria; RNA, Ribosomal, 16S
PubMed: 37158607
DOI: 10.7554/eLife.83152 -
Viruses Mar 2023The mucociliary airway epithelium lines the human airways and is the primary site of host-environmental interactions in the lung. Following virus infection, airway...
The mucociliary airway epithelium lines the human airways and is the primary site of host-environmental interactions in the lung. Following virus infection, airway epithelial cells initiate an innate immune response to suppress virus replication. Therefore, defining the virus-host interactions of the mucociliary airway epithelium is critical for understanding the mechanisms that regulate virus infection, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Non-human primates (NHP) are closely related to humans and provide a model to study human disease. However, ethical considerations and high costs can restrict the use of in vivo NHP models. Therefore, there is a need to develop in vitro NHP models of human respiratory virus infection that would allow for rapidly characterizing virus tropism and the suitability of specific NHP species to model human infection. Using the olive baboon (), we have developed methodologies for the isolation, in vitro expansion, cryopreservation, and mucociliary differentiation of primary fetal baboon tracheal epithelial cells (FBTECs). Furthermore, we demonstrate that in vitro differentiated FBTECs are permissive to SARS-CoV-2 infection and produce a potent host innate-immune response. In summary, we have developed an in vitro NHP model that provides a platform for the study of SARS-CoV-2 infection and other human respiratory viruses.
Topics: Animals; Humans; SARS-CoV-2; Host Microbial Interactions; COVID-19; Papio; Epithelial Cells; Lung
PubMed: 37112842
DOI: 10.3390/v15040862 -
Evolution; International Journal of... Jun 2023Affiliative social behaviors are linked to fitness components in multiple species. However, the role of genetic variance in shaping such behaviors remains largely...
Affiliative social behaviors are linked to fitness components in multiple species. However, the role of genetic variance in shaping such behaviors remains largely unknown, limiting our understanding of how affiliative behaviors can respond to natural selection. Here, we employed the "animal model" to estimate environmental and genetic sources of variance and covariance in grooming behavior in the well-studied Amboseli wild baboon population. We found that the tendency for a female baboon to groom others ("grooming given") is heritable (h2 = 0.22 ± 0.048), and that several environmental variables-including dominance rank and the availability of kin as grooming partners-contribute to variance in this grooming behavior. We also detected small but measurable variance due to the indirect genetic effect of partner identity on the amount of grooming given within dyadic grooming partnerships. The indirect and direct genetic effects for grooming given were positively correlated (r = 0.74 ± 0.09). Our results provide insight into the evolvability of affiliative behavior in wild animals, including the possibility for correlations between direct and indirect genetic effects to accelerate the response to selection. As such they provide novel information about the genetic architecture of social behavior in nature, with important implications for the evolution of cooperation and reciprocity.
Topics: Animals; Female; Social Behavior; Primates; Animals, Wild; Grooming; Papio; Social Dominance
PubMed: 37094802
DOI: 10.1093/evolut/qpad066 -
Royal Society Open Science Apr 2023Quantification of activity budgets is pivotal for understanding how animals respond to changes in their environment. Social grooming is a key activity that underpins...
Quantification of activity budgets is pivotal for understanding how animals respond to changes in their environment. Social grooming is a key activity that underpins various social processes with consequences for health and fitness. Traditional methods use direct (focal) observations to calculate grooming rates, providing systematic but sparse data. Accelerometers, in contrast, can quantify activity budgets continuously but have not been used to quantify social grooming. We test whether grooming can be accurately identified using machine learning (random forest model) trained on labelled acceleration data from wild chacma baboons (). We successfully identified giving and receiving grooming with high precision (81% and 91%) and recall (87% and 79%). Giving grooming was associated with a distinct rhythmical signal along the surge axis. Receiving grooming had similar acceleration signals to resting, and thus was more difficult to assign. We applied our machine learning model to = 680 collar data days from = 12 baboons and found that grooming rates obtained from accelerometers were significantly and positively correlated with direct observation rates for giving but not receiving grooming. The ability to collect continuous grooming data in wild populations will allow researchers to re-examine and expand upon long-standing questions regarding the formation and function of grooming bonds.
PubMed: 37063984
DOI: 10.1098/rsos.221103 -
Hormones and Behavior Jun 2023Animals have finite energy reserves for growth, survival, and reproduction and must maintain a stable energy balance. Measuring energy balance in the wild, however, is...
Animals have finite energy reserves for growth, survival, and reproduction and must maintain a stable energy balance. Measuring energy balance in the wild, however, is beset with methodological challenges. Quantification of urinary C-peptide (uCP), a proxy for insulin secretion, has enabled researchers to non-invasively estimate energy balance, and positive relationships between uCP levels and energy intake have been documented in numerous non-human primates. Comparatively few studies show that, consistent with insulin physiology, energy expenditure also alters levels of uCP. The timescale and extent of this relationship, however, remains unclear given the reliance on crude measures of activity and inferred energy expenditure. Here, for the first time, we test for effects of accelerometer-derived Vectorial Dynamic Body Acceleration (VeDBA) - a continuous measure of physical activity energy expenditure - on urinary C-peptide (uCP) levels in n = 12 wild chacma baboons (Papio ursinus). Applying a model selection approach, we show that VeDBA summed over short timescales (30 min to 1 h) prior to urine collection was negatively associated with uCP levels. Using the acceleration-based time individuals spent 'non-stationary' (i.e. locomoting) prior to urine collection as a predictor - instead of summed VeDBA - revealed similar but less clear results. Overall, the negative relationship between VeDBA and uCP levels highlights the importance of quantifying physical activity energy expenditure when using uCP measures to estimate energy balance and has potential implications for the field of energetics accelerometry.
Topics: Animals; Papio ursinus; C-Peptide; Energy Metabolism; Acceleration; Accelerometry
PubMed: 37031555
DOI: 10.1016/j.yhbeh.2023.105355 -
Genes Feb 2023Baboons (genus ) are an intriguing study system to investigate complex evolutionary processes and the evolution of social systems. An increasing number of studies over... (Review)
Review
Baboons (genus ) are an intriguing study system to investigate complex evolutionary processes and the evolution of social systems. An increasing number of studies over the last 20 years has shown that considerable incongruences exist between phylogenies based on morphology, mitochondrial, and nuclear sequence data of modern baboons, and hybridization and introgression have been suggested as the main drivers of these patterns. Baboons, therefore, present an excellent opportunity to study these phenomena and their impact on speciation. Advances both in geographic and genomic coverage provide increasing details on the complexity of the phylogeography of baboons. Here, we compile the georeferenced genetic data of baboons and review the current knowledge on baboon phylogeny, discuss the evolutionary processes that may have shaped the patterns that we observe today, and propose future avenues for research.
Topics: Animals; Papio; Phylogeny; Phylogeography; Hybridization, Genetic; Genomics
PubMed: 36980887
DOI: 10.3390/genes14030614 -
Emerging Infectious Diseases Apr 2023Hamadryas baboons (Papio hamadryas) may transmit zoonotic vector-borne pathogens to visitors and workers frequenting zoological parks. We molecularly screened 33 baboons...
Hamadryas baboons (Papio hamadryas) may transmit zoonotic vector-borne pathogens to visitors and workers frequenting zoological parks. We molecularly screened 33 baboons for vector-borne pathogens. Three (9.1%) of 33 animals tested positive for Rickettsia conorii subspecies israelensis. Clinicians should be aware of potential health risks from spatial overlapping between baboons and humans.
Topics: Animals; Humans; Rickettsia conorii; Rickettsia; Papio
PubMed: 36958035
DOI: 10.3201/eid2904.221176 -
Journal of Developmental Origins of... Jun 2023Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days...
Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.
Topics: Pregnancy; Animals; Female; Fetal Development; Papio; Nutrients; Liver; Fatty Acids
PubMed: 36924159
DOI: 10.1017/S204017442300003X -
Blood Advances Aug 2023Increased fetal hemoglobin (HbF) levels reduce the symptoms of sickle cell disease (SCD) and increase the lifespan of patients. Because curative strategies for bone...
Increased fetal hemoglobin (HbF) levels reduce the symptoms of sickle cell disease (SCD) and increase the lifespan of patients. Because curative strategies for bone marrow transplantation and gene therapy technologies remain unavailable to a large number of patients, the development of a safe and effective pharmacological therapy that increases HbF offers the greatest potential for disease intervention. Although hydroxyurea increases HbF, a substantial proportion of patients fail to demonstrate an adequate response. Pharmacological inhibitors of DNA methyltransferase (DNMT1) and lysine-specific demethylase 1A (LSD1), 2 epigenome-modifying enzymes associated with the multiprotein corepressor complex recruited to the repressed γ-globin gene, are powerful in vivo inducers of HbF. The hematological side effects of these inhibitors limit feasible clinical exposures. We evaluated whether administering these drugs in combination could reduce the dose and/or time of exposure to any single agent to minimize adverse effects, while achieving additive or synergistic increases in HbF. The DNMT1 inhibitor decitabine (0.5 mg/kg per day) and the LSD1 inhibitor RN-1 (0.25 mg/kg per day) administered in combination 2 days per week produced synergistic increases in F-cells, F-reticulocytes, and γ-globin messenger RNA in healthy baboons. Large increases in HbF and F-cells were observed in healthy, nonanemic, and anemic (phlebotomized) baboons. Combinatorial therapy targeting epigenome-modifying enzymes could thus be a useful strategy for producing larger increases in HbF to modify the clinical course of SCD.
Topics: Humans; Animals; Decitabine; gamma-Globins; Epigenome; Fetal Hemoglobin; Anemia, Sickle Cell; Papio; Histone Demethylases
PubMed: 36884303
DOI: 10.1182/bloodadvances.2022009558 -
Drug and Alcohol Dependence Apr 2023The cannabinoid cannabidiol (CBD) is currently under investigation as a pharmacotherapy for alcohol use disorder. The aim of the present study was to examine whether...
BACKGROUND
The 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).
METHODS
Seven 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.
RESULTS
Across 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.
CONCLUSIONS
In sum, the current data do not support use of pure CBD as an effective pharmacotherapy to reduce ongoing excessive drinking.
Topics: Animals; Male; Humans; Papio; Cannabidiol; Ethanol; Alcoholism; Alcohol Drinking
PubMed: 36871377
DOI: 10.1016/j.drugalcdep.2023.109829