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PLoS Pathogens Apr 2024Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate...
Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate antibody responses in humans and animals that can recognize members of multiple enterovirus species. However, cross protective immunity across multiple enteroviruses is not observed epidemiologically in humans. Here we investigated whether immunization of mice or baboons with inactivated poliovirus or enterovirus virus-like-particles (VLPs) vaccines generates antibody responses that can recognize enterovirus D68 or A71. We found that mice only generated antibodies specific for the antigen they were immunized with, and repeated immunization failed to generate cross-reactive antibody responses as measured by both ELISA and neutralization assay. Immunization of baboons with IPV failed to generate neutralizing antibody responses against enterovirus D68 or A71. These results suggest that a multivalent approach to enterovirus vaccination is necessary to protect against enterovirus disease in vulnerable populations.
Topics: Animals; Mice; Cross Reactions; Antibodies, Viral; Enterovirus Infections; Poliovirus Vaccine, Inactivated; Vaccines, Virus-Like Particle; Antibodies, Neutralizing; Papio; Humans; Poliovirus; Female; Antibody Formation; Enterovirus; Mice, Inbred BALB C; Enterovirus D, Human
PubMed: 38662650
DOI: 10.1371/journal.ppat.1012159 -
PloS One 2023Elevated levels of Fetal Hemoglobin interfere with polymerization of sickle hemoglobin thereby reducing anemia, lessening the severity of symptoms, and increasing life...
Elevated levels of Fetal Hemoglobin interfere with polymerization of sickle hemoglobin thereby reducing anemia, lessening the severity of symptoms, and increasing life span of patients with sickle cell disease. An affordable, small molecule drug that stimulates HbF expression in vivo would be ideally suited to treat the large numbers of SCD patients that exist worldwide. Our previous work showed that administration of the LSD1 (KDM1A) inhibitor RN-1 to normal baboons increased Fetal Hemoglobin (HbF) and was tolerated over a prolonged treatment period. HbF elevations were associated with changes in epigenetic modifications that included increased levels of H3K4 di-and tri-methyl lysine at the γ-globin promoter. While dramatic effects of the loss of LSD1 on hematopoietic differentiation have been observed in murine LSD1 gene deletion and silencing models, the effect of pharmacological inhibition of LSD1 in vivo on hematopoietic differentiation is unknown. The goal of these experiments was to investigate the in vivo mechanism of action of the LSD1 inhibitor RN-1 by determining its effect on γ-globin expression in highly purified subpopulations of bone marrow erythroid cells enriched for varying stages of erythroid differentiation isolated directly from baboons treated with RN-1 and also by investigating the effect of RN1 on the global transcriptome in a highly purified population of proerythroblasts. Our results show that RN-1 administered to baboons targets an early event during erythroid differentiation responsible for γ-globin repression and increases the expression of a limited number of genes including genes involved in erythroid differentiation such as GATA2, GFi-1B, and LYN.
Topics: Animals; Humans; Mice; Anemia, Sickle Cell; Fetal Hemoglobin; gamma-Globins; Gene Expression; Histone Demethylases; Papio anubis
PubMed: 38134183
DOI: 10.1371/journal.pone.0289860 -
Acta Bio-medica : Atenei Parmensis Dec 2023
Topics: Humans; Dyspepsia; History, Early Modern 1451-1600
PubMed: 38054672
DOI: 10.23750/abm.v94i6.15137 -
The American Naturalist Oct 2023AbstractOver the past 50 years, a wealth of testable, often conflicting hypotheses have been generated about the evolution of offspring sex ratio manipulation by...
AbstractOver the past 50 years, a wealth of testable, often conflicting hypotheses have been generated about the evolution of offspring sex ratio manipulation by mothers. Several of these hypotheses have received support in studies of invertebrates and some vertebrate taxa. However, their success in explaining sex ratios in mammalian taxa-especially in primates-has been mixed. Here, we assess the predictions of four different hypotheses about the evolution of biased offspring sex ratios in the baboons of the Amboseli basin in Kenya: the Trivers-Willard, female rank enhancement, local resource competition, and local resource enhancement hypotheses. Using the largest sample size ever analyzed in a primate population ( offspring), we test the predictions of each hypothesis. Overall, we find no support for adaptive biasing of sex ratios. Offspring sex is not consistently related to maternal dominance rank or biased toward the dispersing sex, nor is it predicted by group size, population growth rates, or their interaction with maternal rank. Because our sample size confers power to detect even subtle biases in sex ratio, including modulation by environmental heterogeneity, these results suggest that adaptive biasing of offspring sex does not occur in this population.
Topics: Animals; Female; Papio; Papio cynocephalus; Sex Ratio; Primates; Mammals
PubMed: 37792922
DOI: 10.1086/725886 -
Scientific Reports Jan 2024Although male and female mammals differ in biological traits and functional needs, the contribution of this sexual dimorphism to variations in gut bacteria and fungi...
Although male and female mammals differ in biological traits and functional needs, the contribution of this sexual dimorphism to variations in gut bacteria and fungi (gut microbiota) in relation to habitat type has not been fully examined. To understand whether the combination of sex and habitat affects gut microbiota variation, we analyzed 40 fecal samples of wild yellow baboons (Papio cynocephalus) living in contrasting habitat types (intact, well-protected vs. fragmented, less protected forests) in the Udzungwa Mountains of Tanzania. Sex determination was performed using the marker genes SRY (Sex-determining Region Y) and DDX3X-DDX3Y (DEAD-Box Helicase 3). Samples were attributed to 34 individuals (19 females and 15 males) belonging to five social groups. Combining the results of sex determination with two amplicon sequencing datasets on bacterial (V1-V3 region of the 16S rRNA gene) and fungal (ITS2) gut communities, we found that overall, baboon females had a significantly higher gut bacterial richness compared to males. Beta diversity estimates indicated that bacterial composition was significantly different between males and females, and this was true for individuals from both well- and less protected forests. Our results highlight the combined role of sex and habitat type in shaping variation in gut microbial communities in wild non-human primates.
Topics: Female; Male; Animals; Papio cynocephalus; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Genes, sry; Forests; Papio; Mammals
PubMed: 38195759
DOI: 10.1038/s41598-023-50126-z -
Cell Genomics Mar 2024Understanding how genetic variation impacts gene expression is a major goal of genomics; however, only a fraction of disease-associated loci have been demonstrated to...
Understanding how genetic variation impacts gene expression is a major goal of genomics; however, only a fraction of disease-associated loci have been demonstrated to impact gene expression when cells are in an unperturbed "steady state." In this issue of Cell Genomics, Lin et al. investigate how exposure to a particular cellular context (i.e., a high-cholesterol, high-fat diet) can enhance our ability to identify new regulatory variants through longitudinal sampling of three tissue types in the baboon.
Topics: Animals; Papio; Quantitative Trait Loci; Diet, High-Fat; Genomics
PubMed: 38484702
DOI: 10.1016/j.xgen.2024.100524 -
Proceedings of the National Academy of... Mar 2024The early-life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early-life...
The early-life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early-life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early-life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early-life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early-life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early-life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early-life effects on fitness-related traits.
Topics: Animals; DNA Methylation; Adverse Childhood Experiences; Nucleotide Motifs; Biological Assay; Papio
PubMed: 38442181
DOI: 10.1073/pnas.2309469121 -
Ecology and Evolution Mar 2024Olive baboons () use fixed, secure, and naturally occurring sleeping sites such as tall trees and rocky cliffs, as protection from predators and often show a selection...
Olive baboons () use fixed, secure, and naturally occurring sleeping sites such as tall trees and rocky cliffs, as protection from predators and often show a selection preference for particular trees or rocky cliff faces. We documented olive baboons' adoption of recently constructed high-tension electrical transmission towers (pylons) as a novel type of sleeping site in Laikipia, Kenya. The use of pylons suggests that the greatest potential benefits may include reduced parasite exposure and predation avoidance. Thermoregulation and feeding efficiency are not supported as benefits because pylons increase baboons' exposure to wind and cool nighttime temperatures and the pylons were constructed in locations independent of established feeding sites. These observations advance our understanding of olive baboon sleeping site selection in a changing landscape.
PubMed: 38481758
DOI: 10.1002/ece3.11164 -
Xenotransplantation 2024Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the...
Hemodynamics in pig-to-baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth.
INTRODUCTION
Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth.
METHODS
We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously.
RESULTS
Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation.
CONCLUSION
The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size.
Topics: Animals; Transplantation, Heterologous; Heart Transplantation; Swine; Hemodynamics; Heterografts; Papio; Graft Survival; Transplantation, Heterotopic; Animals, Genetically Modified; Graft Rejection; Humans
PubMed: 38864375
DOI: 10.1111/xen.12841 -
PLoS Computational Biology Jan 2024As part of a long-term research project aiming at generating a biomechanical model of a fossil human tongue from a carefully designed 3D Finite Element mesh of a living...
As part of a long-term research project aiming at generating a biomechanical model of a fossil human tongue from a carefully designed 3D Finite Element mesh of a living human tongue, we present a computer-based method that optimally registers 3D CT images of the head and neck of the living human into similar images of another primate. We quantitatively evaluate the method on a baboon. The method generates a geometric deformation field which is used to build up a 3D Finite Element mesh of the baboon tongue. In order to assess the method's ability to generate a realistic tongue from bony structure information alone, as would be the case for fossil humans, its performance is evaluated and compared under two conditions in which different anatomical information is available: (1) combined information from soft-tissue and bony structures; (2) information from bony structures alone. An Uncertainty Quantification method is used to evaluate the sensitivity of the transformation to two crucial parameters, namely the resolution of the transformation grid and the weight of a smoothness constraint applied to the transformation, and to determine the best possible meshes. In both conditions the baboon tongue morphology is realistically predicted, evidencing that bony structures alone provide enough relevant information to generate soft tissue.
Topics: Animals; Humans; Hominidae; Fossils; Skull; Tongue; Papio; Finite Element Analysis; Computer Simulation
PubMed: 38252664
DOI: 10.1371/journal.pcbi.1011808