-
Immunity, Inflammation and Disease Jun 2024Major histocompatibility complex (MHC) class II molecules expressed on B cells, monocytes and dendritic cells present processed peptides to CD4 T cells as one of the...
BACKGROUND
Major histocompatibility complex (MHC) class II molecules expressed on B cells, monocytes and dendritic cells present processed peptides to CD4 T cells as one of the mechanisms to combat infection and inflammation.
AIM
To study MHC II expression in a variety of nonhuman primate species, including New World (NWM) squirrel monkeys (Saimiri boliviensis boliviensis), owl monkeys (Aotus nancymae), common marmosets (Callithrix spp.), and Old World (OWM) rhesus (Macaca mulatta), baboons (Papio anubis).
METHODS
Two clones of cross-reactive mouse anti-human HLADR monoclonal antibodies (mAb) binding were analyzed by flow cytometry to evaluate MHC II expression on NHP immune cells, including T lymphocytes in whole blood (WB) and peripheral blood mononuclear cells (PBMC).
RESULTS
MHC class II antibody reactivity is seen with CD20 B cells, CD14 monocytes and CD3 T lymphocytes. Specific reactivity with both clones was demonstrated in T lymphocytes: this reactivity was not inhibited by purified CD16 antibody but was completely inhibited when pre-blocked with purified unconjugated MHC II antibody. Freshly prepared PBMC also showed reactivity with T lymphocytes without any stimulation. Interestingly, peripheral blood from rhesus macaques and olive baboons (OWM) showed no such T lymphocyte associated MHCII antibody reactivity.
DISCUSSION & CONCLUSION
Our results from antibody (MHC II) reactivity clearly show the potential existence of constitutively expressed (with no stimulation) MHC II molecules on T lymphocytes in new world monkeys. These results suggest that additional study is warranted to evaluate the functional and evolutionary significance of these finding and to better understand MHC II expression on T lymphocytes in new world monkeys.
Topics: Animals; Histocompatibility Antigens Class II; HLA-DR Antigens; T-Lymphocytes; Humans; Macaca mulatta; Antibodies, Monoclonal; B-Lymphocytes; Saimiri; Callithrix; Flow Cytometry; Papio anubis; Platyrrhini
PubMed: 38923761
DOI: 10.1002/iid3.1318 -
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 -
Nature Communications Jun 2024The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready...
The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready brain. However, studies have reported a similar structural PT left-asymmetry not only in various adult non-human primates, but also in newborn baboons. Its shared functional links with language are not fully understood. Here we demonstrate using previously obtained MRI data that early detection of PT left-asymmetry among 27 newborn baboons (Papio anubis, age range of 4 days to 2 months) predicts the future development of right-hand preference for communicative gestures but not for non-communicative actions. Specifically, only newborns with a larger left-than-right PT were more likely to develop a right-handed communication once juvenile, a contralateral brain-gesture link which is maintained in a group of 70 mature baboons. This finding suggests that early PT asymmetry may be a common inherited prewiring of the primate brain for the ontogeny of ancient lateralised properties shared between monkey gesture and human language.
Topics: Animals; Functional Laterality; Gestures; Animals, Newborn; Magnetic Resonance Imaging; Female; Male; Papio anubis; Temporal Lobe; Language
PubMed: 38839754
DOI: 10.1038/s41467-024-47277-6 -
American Journal of Veterinary Research May 2024Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates.
OBJECTIVE
Present an approach to the safe and efficient provision of anesthesia and birth control measures to a large group of primates.
ANIMALS
98 hamadryas baboons (Papio hamadryas) held in a German zoological institution.
METHODS
A group of 12 veterinarians, 2 zookeepers, and 6 volunteers anesthetized all animals within 2 days. The baboons were orally premedicated with midazolam (0.1 to 0.5 mg/kg) and anesthetized with medetomidine (40 to 60 µg/kg, IM) and ketamine (2 to 4 mg/kg, IM); isoflurane at rates of 1.5% to 2% was used for maintaining anesthesia if necessary. All animals received a physical examination, prophylactic medication, and tuberculin testing. For population management, the animals received a contraceptive implant (adult females), orchiectomy (young males), or vasectomy (breeding males). Young males received intratesticular blocks with lidocaine. All animals received atipamezole (125 to 150 µg/kg) before recovery.
RESULTS
Premedication resulted in anxiolysis, which facilitated separating and darting. Median time from darting to access to the animal was 10 minutes. Mean anesthetic times were 25 minutes for females and 55 minutes for males. The depth of anesthesia was appropriate for the procedures. No fatalities were recorded. One animal was injured by other baboons but recovered after treatment.
CLINICAL RELEVANCE
Health management and birth control measures are necessary in baboon troops under human care. Anesthesia and/or contraception of individual animals often leads to intraspecific aggression. This case series describes how to provide anesthesia and contraception to an entire troop as an alternative approach that can be adopted to future similar interventions.
PubMed: 38744308
DOI: 10.2460/ajvr.23.12.0274 -
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 -
Proceedings of the National Academy of... Mar 2024Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the evolutionary...
Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the evolutionary dynamics within hybrid populations that underlie these patterns have been lacking. Due to the clock-like effect of recombination in hybrids breaking up parental haplotypes, drift and selection produce predictable patterns of ancestry variation at varying spatial genomic scales through time. Here, we develop methods based on the Discrete Wavelet Transform to study the genomic scale of local ancestry variation and its association with recombination rates and show that these methods capture temporal dynamics of drift and genome-wide selection after hybridization. We apply these methods to published datasets from hybrid populations of swordtail fish () and baboons () and to inferred Neanderthal introgression in modern humans. Across systems, upward of 20% of variation in local ancestry at the broadest genomic scales can be attributed to systematic selection against introgressed alleles, consistent with strong selection acting on early-generation hybrids. Signatures of selection at fine genomic scales suggest selection over longer time scales; however, we suggest that our ability to confidently infer selection at fine scales is likely limited by inherent biases in current methods for estimating local ancestry from contiguous segments of genomic similarity. Wavelet approaches will become widely applicable as genomic data from systems with introgression become increasingly available and can help shed light on generalities of the genomic consequences of interspecific hybridization.
Topics: Animals; Humans; Genome; Genomics; Hybridization, Genetic; Nucleic Acid Hybridization; Haplotypes; Neanderthals; Selection, Genetic
PubMed: 38489387
DOI: 10.1073/pnas.2309168121 -
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 -
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 -
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 -
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