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Scientific Reports Mar 2023Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable...
Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, -451a, -191-5p, -148a-3p, -17-5p, -378c, and -144-3p) were differentially expressed between paired fatty streak lesion and no-lesion sites of the tissue, and 27 miRNAs (e.g., miR-92a-3p, -5001, -342-3p, miR-28-3p, -21-5p, -221-3p, 146a-5p, and -16-5p) in fibrous plaques. The expression of 14 blood miRNAs significantly correlated with extent of lesions and the number of plaques. We identified coordinately regulated miRNA-gene networks in which miR-17-5p and miR-146a-5p are central hubs and miR-5001 and miR-7975 are potentially novel miRNAs associated with early atherosclerosis. In summary, we have identified miRNAs expressed in lesions and in blood that correlate with lesion burden and are potential therapeutic targets and biomarkers. These findings are a first step in elucidating miRNA regulated molecular mechanisms that underlie early atherosclerosis in a baboon model, enabling translation of our findings to humans.
Topics: Animals; Humans; Atherosclerosis; Aorta, Abdominal; Biomarkers; Diet, High-Fat; MicroRNAs; Papio; Plaque, Amyloid
PubMed: 36859458
DOI: 10.1038/s41598-023-29074-1 -
Nature Communications Feb 2023SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant...
SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.
Topics: Animals; Humans; Mice; Antibodies, Neutralizing; COVID-19; Nanoparticles; Papio; SARS-CoV-2; Vaccines; COVID-19 Vaccines
PubMed: 36854666
DOI: 10.1038/s41467-022-35606-6 -
STAR Protocols Mar 2023Primary human mammary epithelial cells (pHMECs) are known to be remarkably difficult to engineer genetically. Here, we present a protocol for efficient transduction of...
Primary human mammary epithelial cells (pHMECs) are known to be remarkably difficult to engineer genetically. Here, we present a protocol for efficient transduction of pHMECs using a baboon retroviral envelope glycoprotein for pseudotyping of lentiviral vectors (BaEV-LVs). We describe the preparation of the BaEV-LVs, the isolation of pHMECs from breast samples, and the subsequent transduction of pHMECs. We also detail the use of CRISPRi technology to efficiently silence gene expression in pHMECs, which can then be used for functional assays. For complete details on the use and execution of this protocol, please refer to Richart et al. (2022)..
Topics: Animals; Humans; Lentivirus; Genetic Vectors; Viral Envelope Proteins; Transduction, Genetic; Papio; Epithelial Cells
PubMed: 36853718
DOI: 10.1016/j.xpro.2023.102055 -
Veterinary Sciences Feb 2023The study aims to describe the anesthetic and airway management of baboons undergoing laparoscopic salpingectomy with a laryngeal mask airway (LMA) device. Eleven...
The study aims to describe the anesthetic and airway management of baboons undergoing laparoscopic salpingectomy with a laryngeal mask airway (LMA) device. Eleven baboons received tiletamine-zolazepam and medetomidine; anesthesia was induced with propofol. An LMA was positioned for oxygen and isoflurane administration in spontaneous respiration. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), end tidal carbon dioxide (EtCO), minute volume (MV), and peripheral hemoglobin oxygen saturation (SpO) were recorded before (PREPP) and immediately after abdomen insufflation (PP1), at 10 (PP2), 20 (PP3), and 30 (PP4) minutes during pneumoperitoneum, and after (POSTPP) pneumoperitoneum. The respiratory rate was significantly higher at all times compared to PREPP. The end tidal carbon dioxide concentration was significantly higher at PP2, PP3, PP4, and POSTPP, compared to the previous times. The higher values for RR and EtCO were registered at PP4: 22.7 (95% CI 17.6-27.8) breaths/min and 57.9 (95% CI 51.9-63.8) mmHg, respectively. The minute volume was significantly higher at PP4 and POSTPP compared to the other times. The higher value for MV was registered at POSTPP (269.1 (95% CI 206.1-331.8) mL/kg/min). This protocol is suitable for baboons undergoing laparoscopic salpingectomy. The LMA was easy to insert and allowed for good ventilation, gas exchange, and delivery of the anesthetic in spontaneous breathing baboons.
PubMed: 36851462
DOI: 10.3390/vetsci10020158 -
Neurobiology of Aging May 2023Age-related changes in cognition, brain morphology, and behavior are exhibited in several primate species. Baboons, like humans, naturally develop Alzheimer's...
Age-related changes in cognition, brain morphology, and behavior are exhibited in several primate species. Baboons, like humans, naturally develop Alzheimer's disease-like pathology and cognitive declines with age and are an underutilized model for studies of aging. To determine age-related differences in gray matter covariation of 89 olive baboons (Papio anubis), we used source-based morphometry (SBM) to analyze data from magnetic resonance images. We hypothesized that we would find significant age effects in one or more SBM components, particularly those which include regions influenced by age in humans and other nonhuman primates (NHPs). A multivariate analysis of variance revealed that individual weighted gray matter covariation scores differed across the age classes. Elderly baboons contributed significantly less to gray matter covariation components including the brainstem, superior parietal cortex, thalamus, and pallidum compared to juveniles, and middle and superior frontal cortex compared to juveniles and young adults (p < 0.05). Future studies should examine the relationship between the changes in gray matter covariation reported here and age-related cognitive decline.
Topics: Humans; Animals; Aged; Gray Matter; Papio anubis; Brain; Papio; Cerebral Cortex; Magnetic Resonance Imaging
PubMed: 36827943
DOI: 10.1016/j.neurobiolaging.2023.01.005 -
Xenotransplantation Mar 2023With pig kidney xenotransplantation nearing clinical reality, it is imperative to measure pig kidney function in the graft recipients. Our aims were (i) to compare...
With pig kidney xenotransplantation nearing clinical reality, it is imperative to measure pig kidney function in the graft recipients. Our aims were (i) to compare inulin clearance after a short intravenous (IV) bolus with steady-state inulin IV infusion, (ii) to use this method to measure the glomerular filtration rate (GFR), and (iii) to determine the tubular secretory function using cefoxitin in a pig-to-baboon renal transplant model. A short IV infusion of inulin and cefoxitin were followed by a maintenance IV infusion of inulin over 5 h in seven healthy baboons, three healthy pigs, and five baboons after bilateral native nephrectomy and intra-abdominal pig renal transplantation. Blood and urine samples were collected. Serum and urinary inulin and serum cefoxitin concentrations measured by validated assays were used to calculate GFR and renal secretion. GFR calculated were similar by both methods. The body weight normalized total body clearance of inulin was similar in pigs and baboons despite differences in absolute clearances. Pig kidney transplanted into baboons provided similar clearance in baboons when normalized to baboon body weight and sustained filtration and secretory functions. The study documented that pig kidneys support the physiologic needs of baboons and are likely to support human recipients as well.
Topics: Animals; Swine; Humans; Kidney Transplantation; Papio; Inulin; Cefoxitin; Transplantation, Heterologous; Kidney
PubMed: 36820525
DOI: 10.1111/xen.12795 -
Philosophical Transactions of the Royal... Apr 2023Most studies of collective animal behaviour rely on short-term observations, and comparisons of collective behaviour across different species and contexts are rare. We...
Most studies of collective animal behaviour rely on short-term observations, and comparisons of collective behaviour across different species and contexts are rare. We therefore have a limited understanding of intra- and interspecific variation in collective behaviour over time, which is crucial if we are to understand the ecological and evolutionary processes that shape collective behaviour. Here, we study the collective motion of four species: shoals of stickleback fish (), flocks of homing pigeons (), a herd of goats () and a troop of chacma baboons (). First, we describe how local patterns (inter-neighbour distances and positions), and group patterns (group shape, speed and polarization) during collective motion differ across each system. Based on these, we place data from each species within a 'swarm space', affording comparisons and generating predictions about the collective motion across species and contexts. We encourage researchers to add their own data to update the 'swarm space' for future comparative work. Second, we investigate intraspecific variation in collective motion over time and provide guidance for researchers on when observations made over different time scales can result in confident inferences regarding species collective motion. This article is part of a discussion meeting issue 'Collective behaviour through time'.
Topics: Animals; Columbidae; Behavior, Animal; Motion; Smegmamorpha; Biological Evolution
PubMed: 36802781
DOI: 10.1098/rstb.2022.0068 -
American Journal of Biological... Mar 2022To assess manifestations of metabolic bone disease (MBD) and their potential environmental and phenotypic factors in captive and non-captive baboon (Papio spp.)...
OBJECTIVES
To assess manifestations of metabolic bone disease (MBD) and their potential environmental and phenotypic factors in captive and non-captive baboon (Papio spp.) specimens.
MATERIALS AND METHODS
Our sample consisted of 160 baboon specimens at the Smithsonian's National Museum of Natural History accessioned from 1890 to 1971. Combining cranial indicators of MBD and the museum's historical data, we examined factors contributing to likely instances of MBD. We used binomial-family generalized linear models to assess differences in MBD frequency by environment (captive, non-captive), specimen accession year, and skin color (light, medium, dark).
RESULTS
Indicators of MBD were most frequently observed in captive baboons, with a decrease in MBD frequency over time. Fifteen non-captive individuals showed indicators of MBD, which are the first published cases of MBD in non-captive nonhuman primates (NHPs) to our knowledge. The most common MBD indicators were bone porosity (n = 35) and bone thickening/enlargement (n = 35). Fibrous osteodystrophy was observed frequently in our sample, likely relating to nutritional deficiencies. We found no association between exposed facial skin color variation and MBD.
CONCLUSIONS
Our findings are consistent with historical accounts of MBD prevalence in captive facilities, especially earlier in the 20th century. A decrease in MBD prevalence later in the 20th century likely reflects improvements in housing, diet, and veterinary care in captive settings. Causes of MBD development in non-captive baboons should be further explored, as understanding the potential health impacts that anthropogenic environments impose on NHPs is imperative as humans increasingly alter the natural world in the 21st century.
Topics: Animals; Humans; Papio; Museums; Bone Diseases, Metabolic
PubMed: 36787760
DOI: 10.1002/ajpa.24450 -
Journal of Virological Methods Apr 2023The development of hematopoietic stem cell (HSCs) gene therapy for DNA repair disorders, such as Fanconi anemia and Bloom syndrome, is challenging because of the...
The development of hematopoietic stem cell (HSCs) gene therapy for DNA repair disorders, such as Fanconi anemia and Bloom syndrome, is challenging because of the induction of HSCs apoptosis by cytokine stimulation. Although the Baboon envelope pseudotyped lentiviral vector (BaEV-Rless-LV) has been reported as a non-stimulatory gene transfer tool, the virus titer of BaEV-Rless-LV is too low for use in clinical applications. Transfected 293 T cells with helper plasmids, including the BaEV-Rless plasmid, showed morphological changes, such as syncytium formation and detachment. To establish a novel protocol for producing a high titer of BaEV-Rless-LV, we optimized three aspects of a basic virus production protocol by focusing on modifying culture conditions and the use of reagents: the virus titer increased 3-fold when the amount of BaEV-Rless plasmid was increased 1.2-fold; the highest titer was obtained when the viral supernatant was harvested at 48-h post-transfection, despite complete syncytium formation and detachment of the 293 T cells; and the use of poly-L-lysine-coated culture plates to enhance the adhesion and proliferation of 293 T cells and prevent detachment doubled the titer. Collectively, our novel protocol resulted in a 10-fold titer increase compared to the basic protocol and may be useful in clinical applications for treating DNA repair disorders.
Topics: Animals; Lentivirus; Plasmids; Transfection; Hematopoietic Stem Cells; Papio; Giant Cells; Genetic Vectors; Transduction, Genetic
PubMed: 36739979
DOI: 10.1016/j.jviromet.2023.114689 -
Stem Cells Translational Medicine Mar 2023Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia....
Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms.
Topics: Infant, Newborn; Animals; Humans; Lung; Bronchopulmonary Dysplasia; Infant, Premature; Primates; Mesenchymal Stem Cells
PubMed: 36724000
DOI: 10.1093/stcltm/szac088