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Scientific Reports Dec 2023Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated...
Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated intravascular coagulation, and their potential treatment with novel drugs. Thrombin generation is vital for these models, and an important potential therapeutic target. We investigated the thrombin generation profile of the Chacma baboon (Papio ursinus - a common pre-clinical model) including the effects of sex and ABO blood group. Thrombin generation curves, lag times, peak heights, times-to-peak, velocity indexes and Endogenous Thrombin Potentials (ETPs) of 40 adult Chacma baboons were assessed and compared with normal human plasma, using a low concentration of tissue factor (1 pM) and phospholipids. Reference intervals were calculated, and results compared between O and non-O ABO blood groups, and between males and females. Lag times of all baboons fell within the human reference interval. Most animals (n = 32; 80%) had times-to-peak above, and velocity indexes and peak heights markedly below (n = 27; 68%) the human range. However, 97.5% of baboons had an ETP above the human reference interval, indicating greater overall thrombin generation. ABO blood group had no effect, but males (n = 14; 35%) had less potent thrombin generation than females (n = 26; 65%), with significantly longer lag times (p = 0.0475), lower peak thrombin concentrations (p = 0.0203), and lower ETPs (p = 0.0238). Chacma baboons have greater overall endogenous thrombin generation potentials than humans, which is even more prominent in females. This should be considered when designing future baboon model experiments involving the haemostatic system, or when evaluating novel therapies in these animals.
Topics: Male; Animals; Female; Humans; Papio ursinus; Thrombin; Hemostatics; ABO Blood-Group System; Papio
PubMed: 38151511
DOI: 10.1038/s41598-023-50341-8 -
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 -
Experimental Physiology Apr 2024Heat stroke is a perilous condition marked by severe hyperthermia and extensive multiorgan dysfunction, posing a considerable risk of mortality if not promptly... (Review)
Review
Heat stroke is a perilous condition marked by severe hyperthermia and extensive multiorgan dysfunction, posing a considerable risk of mortality if not promptly identified and treated. Furthermore, the complex biological mechanisms underlying heat stroke-induced tissue and cell damage across organ systems remain incompletely understood. This knowledge gap has hindered the advancement of effective preventive and therapeutic strategies against this condition. In this narrative review, we synthesize key insights gained over a decade using a translational baboon model of heat stroke. By replicating heat stroke pathology in a non-human primate species that closely resembles humans, we have unveiled novel insights into the pathways of organ injury and cell death elicited by this condition. Here, we contextualize and integrate the lessons learned concerning heat stroke pathophysiology and recovery, areas that are inherently challenging to investigate directly in human subjects. We suggest novel research directions to advance the understanding of the complex mechanisms underlying cell death and organ injury. This may lead to precise therapeutic strategies that benefit individuals suffering from this debilitating condition.
Topics: Animals; Humans; Papio; Heat Stroke; Fever
PubMed: 38124439
DOI: 10.1113/EP091586 -
Journal of Medical Primatology Feb 2024In recent times, global viral outbreaks and diseases, such as COVID-19 (SARS-CoV-2), Zika (ZIKV), monkeypox (MPOX), Ebola (EBOV), and Marburg (MARV), have been... (Review)
Review
In recent times, global viral outbreaks and diseases, such as COVID-19 (SARS-CoV-2), Zika (ZIKV), monkeypox (MPOX), Ebola (EBOV), and Marburg (MARV), have been extensively documented. Swiftly deciphering the mechanisms underlying disease pathogenesis and devising vaccines or therapeutic interventions to curtail these outbreaks stand as paramount imperatives. Amidst these endeavors, animal models emerge as pivotal tools. Among these models, non-human primates (NHPs) hold a position of particular importance. Their proximity in evolutionary lineage and physiological resemblances to humans render them a primary model for comprehending human viral infections. This review encapsulates the pivotal role of various NHP species-such as rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), african green monkeys (Chlorocebus sabaeus/aethiops), pigtailed macaques (Macaca nemestrina/Macaca leonina), baboons (Papio hamadryas/Papio anubis), and common marmosets (Callithrix jacchus)-in investigations pertaining to the abovementioned viral outbreaks. These NHP models play a pivotal role in illuminating key aspects of disease dynamics, facilitating the development of effective countermeasures, and contributing significantly to our overall understanding of viral pathogenesis.
Topics: Animals; Chlorocebus aethiops; SARS-CoV-2; COVID-19; Macaca mulatta; Zika Virus Infection; Zika Virus; Virus Diseases; Macaca fascicularis; Papio; Papio anubis; Disease Models, Animal
PubMed: 38084001
DOI: 10.1111/jmp.12689 -
PloS One 2023Since predynastic times, baboons (Papio hamadryas and Papio anubis) were important in ancient Egypt for ritual and religious purposes. These species did not occur...
Since predynastic times, baboons (Papio hamadryas and Papio anubis) were important in ancient Egypt for ritual and religious purposes. These species did not occur naturally in Egypt and therefore had to be imported, but little is known about their exact provenance and the conditions in which they were kept through time. Here, we analyse the skeletal remains of a collection of baboon mummies coming from Thebes (Egypt), representing a minimum of 36 individuals, from a palaeopathological and demographic point of view. The pathological cases are described, figured where relevant, and the discussion attempts to understand their aetiology. The prevalence of the different types of deformations and pathologies is compared with that of other captive baboon populations from more or less contemporary (Tuna el-Gebel and Saqqara) or older (predynastic Hierakonpolis) sites. This is combined with observations on the age and sex distribution and the proportion of hamadryas and anubis baboons to draw conclusions about the conditions of keeping, possible breeding on-site, provenance of the animals and the trade routes used for import. As in Tuna el-Gebel and Saqqara, the baboons from Gabbanat el-Qurud suffered from numerous metabolic diseases due to chronic lack of sunlight and an unbalanced diet. This and the demographic data suggest that there was a local breeding population derived from animals captured downstream from the Sudanese Nile Valley (for anubis) and from the Horn of Africa or the southern part of the Arabian Peninsula (for hamadryas). A new series of radiocarbon dates is provided, placing the baboons from Gabbanat el-Qurud between the end of the Third Intermediate Period and the beginning of the Late Period.
Topics: Humans; Animals; Papio; Papio hamadryas; Egypt; Plant Breeding; Papio anubis; Demography
PubMed: 38055690
DOI: 10.1371/journal.pone.0294934 -
Acta Bio-medica : Atenei Parmensis Dec 2023
Topics: Humans; Dyspepsia; History, Early Modern 1451-1600
PubMed: 38054672
DOI: 10.23750/abm.v94i6.15137 -
Veterinary Research Communications Apr 2024The presence of HSPs in female reproductive and their relationship with the steroid hormone fluctuation have been reported in several mammals but not in non-human...
The presence of HSPs in female reproductive and their relationship with the steroid hormone fluctuation have been reported in several mammals but not in non-human primates. The present research dealt with the oviductal expression and localization of the more studied HSPs (60, 70, and 90) as well as the morphological changes in the Hamadryas baboon (Papio hamadryas) during the follicular, preovulatory, and luteal phases of the menstrual cycle. Therefore, western blots, histomorphological, and immunohistochemical analyses were carried out. The results of western blot analysis displayed the lowest HSP expression in the luteal phase. The histomorphology showed that the mucosal epithelium consisted of undifferentiated cuboidal cells in follicular and luteal phases and well-distinguishable columnar ciliated and non-ciliated cells during the preovulatory phase. Immunohistochemistry evidenced that the mucosal epithelium contained cytoplasmic and nuclear HSP60, 70, and 90 immunostaining in the follicular and luteal phases. During the preovulatory phase, the non-ciliated cells showed: (i) cytoplasmic HSP60; (ii) nuclear and cytoplasmic HSP90. Ciliated cells showed cytoplasmic and ciliary HSP70 and ciliary HSP90. The stromal cells and myocytes of muscular layer displayed a decreased cytoplasmic HSP60 in the preovulatory phase and nuclear and low cytoplasmic HSP70 throughout the menstrual cycle. Nuclear HSP90 decreased in ampulla stromal cells and the follicular phase myocytes. These findings indicate that the expression pattern of HSP60,70, and 90 is related to the morphofunctional features of the baboon oviductal ampulla during the menstrual cycle and could represent a referent point for further studies in the oviduct of Primates.
Topics: Female; Animals; Papio hamadryas; Chaperonin 60; Menstrual Cycle; Fallopian Tubes; Epithelium; Mammals; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins
PubMed: 38038815
DOI: 10.1007/s11259-023-10270-3 -
Royal Society Open Science Nov 2023Research in social mammals has revealed the complexity of strategies females use in response to female-female reproductive competition and sexual conflict. One point at...
Research in social mammals has revealed the complexity of strategies females use in response to female-female reproductive competition and sexual conflict. One point at which competition and conflict manifests acutely is during sexual receptivity, indicated by swellings in some primates. Whether females can adjust their sexual receptivity from cycle to cycle to decrease reproductive competition and sexual conflict in response to social pressures has not been tested. As a first step, this study explores whether sexual receptivity duration is predicted by social pressures in wild female chacma baboons (). Given that female baboons face intense reproductive competition and sexual coercion, we predicted that: females could shorten the duration of their sexual receptive period to reduce female-female aggression and male coercion or increase it to access multiple or their preferred male(s). We quantified 157 ovulatory cycles from 46 wild females living in central Namibia recorded over 15 years. We found no support for our hypothesis; however, our analyses revealed a negative correlation between maximal-swelling duration and group size, a proxy of within-group competition. This study provides further evidence that swelling is costly as well as a testable framework for future investigations of 'cycle length manipulation'.
PubMed: 38034125
DOI: 10.1098/rsos.231307 -
Proceedings. Biological Sciences Nov 2023Affiliative social bonds are linked to fitness components in many social mammals. However, despite their importance, little is known about how the tendency to form...
Affiliative social bonds are linked to fitness components in many social mammals. However, despite their importance, little is known about how the tendency to form social bonds develops in young animals, or if the timing of development is heritable and thus can evolve. Using four decades of longitudinal observational data from a wild baboon population, we assessed the environmental determinants of an important social developmental milestone in baboons-the age at which a young animal first grooms a conspecific-and we assessed how the rates at which offspring groom their mothers develops during the juvenile period. We found that grooming development differs between the sexes: female infants groom at an earlier age and reach equal rates of grooming with their mother earlier than males. We also found that age at first grooming for both sexes is weakly heritable ( = 0.043, 95% CI: 0.002-0.110). These results show that sex differences in grooming emerge at a young age; that strong, equitable social relationships between mothers and daughters begin very early in life; and that age at first grooming is heritable and therefore can be shaped by natural selection.
Topics: Humans; Animals; Female; Male; Social Behavior; Mothers; Papio; Sexual Behavior; Sex Characteristics; Grooming; Mammals
PubMed: 37964524
DOI: 10.1098/rspb.2023.1597 -
PloS One 2023In environments with multiple predators, vulnerabilities associated with the spatial positions of group-living prey are non-uniform and depend on the hunting styles of...
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.
Topics: Humans; Animals; Male; Papio anubis; Papio; Predatory Behavior; Geographic Information Systems
PubMed: 37939092
DOI: 10.1371/journal.pone.0287357