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PubMed1977

Cardiovascular and hepatic responses of rhesus macaques to staphylococcal enterotoxin B.

Certain cardiovascular and hepatic functions were measured for a period of 6 to 14 hours in conscious, chaired, male rhesus macaques given (intravenously (IV) or orally) staphylococcal enterotoxin B (SEB). In macaques orally given SEB (1 mg/kg), there was little change in the cardiovascular variables. The half-life of injected indocyanine green was apparently prolonged in macaques given SEB as compared with that in the controls. However, in macaques given SEB (0.05 or 1.0 mg/kg) by IV injection, there were tachycardia, increase in arterial resistance, and decreases in blood pressure, cardiac output, stroke volume, cardiac work, mean cardiac power, and central blood volume. In addition, mean transit time from caudal vena cava to ascending aorta was prolonged and a simultaneous reduction of hepatic removal of indocyanine green occurred.

Administration, Oral↗
PubMed2026

Expression patterns of risk genes associated with three evolutionarily relevant syndromes in rhesus macaque and human brains.

Depressive disorder (DD), Alzheimer's disease (AD), and schizophrenia (SZ) are evolutionarily relevant traits that disrupt neural networks supporting affect and cognition. While genome-wide association studies have identified risk-related genes for these diseases, how the expression of these genes compare across species remains unclear. In this study, we examined the spatial and temporal expression of ~2000 disease-associated genes in human and rhesus macaque brains. Distinct cross-species signatures emerged. DD-linked genes showed broad cortical-subcortical expression in humans but were confined to subcortical regions in macaques. The divergent subset was enriched for neuron differentiation, migration, synaptic signalling, and cognition. SZ-linked genes were expressed across cortical-subcortical-cerebellar structures in humans. AD-linked genes showed postnatal cortical-hippocampal macaque expression, and broader cortical-subcortical human expression. Cross-species spatial comparisons revealed a significant negative correlation for DD genes, suggesting a broader spatial distribution of DD-related gene expression in humans, extending to distributed emotion-cognition networks, compared to affective hubs in macaques. SZ genes exhibited a similar, though non-significant, negative trend, while AD genes showed a weak, non-significant correlation, indicating an absence of systematic expression shifts. Together, evolutionary shifts in gene expression may have shaped emotional and cognitive functions in humans, and susceptibility to psychiatric and neurodegenerative disorders.

Animals↗
PubMed2025

A complete and near-perfect rhesus macaque reference genome: lessons from subtelomeric repeats and sequencing bias.

A truly complete, telomere-to-telomere (T2T), and error-free reference genome remains a foundational resource-and long-standing goal-for unbiased comparative and functional genomics. While recent T2T assemblies of humans and other primates have made substantial progress, most still contain thousands of base-level errors, particularly within highly repetitive regions. Here, we present T2T-MMU8v2.0, a near-perfect T2T assembly of the rhesus macaque (Macaca mulatta), representing the highest base-level accuracy reported in a primate genome to date. By employing an optimized ONT-only assembly strategy, we identify subtelomeric satellite-rich regions as the principal bottleneck to improving assembly quality, owing to technological biases in long-read platforms and limitations in current hybrid assembly frameworks. We discover 268 previously unannotated repeat families and resolve ~8 Mbp of SATR satellite arrays, with over 99-fold enrichment in historically misassembled subtelomeric regions. These satellites form four distinct genomic architectures, each with unique SATR satellite composition, segmental duplication organization, and epigenetic signatures, distinct from the subtelomeric architectures observed in hominid genomes. Notably, in contrast to the largely gene-poor subtelomeric regions in African hominids, the SATR architectures in macaques harbor 58 actively transcribed genes, supported by open chromatin and expression data, suggesting gene innovation within these repetitive regions. Functionally, T2T-MMU8v2.0 improves read mappability and accuracy across sequencing platforms, and results in a 19% improvement of transcription start site enrichment scores and 5,821 additional chromatin accessibility peaks on average, thereby enhancing variant detection, regulatory annotation, and transcriptomic resolution in population genetics or single-nucleus studies. Together, this work establishes a new benchmark for genomics, offers a roadmap for resolving complex repetitive regions, and reveals previously unrecognized features of subtelomeric genome structure and evolution.

Journal Article↗
PubMed2025

Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques.

The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-β-CoV vaccines.

Animals↗
PubMed1975

Modification of the response to separation in the infant rhesus macaque through manipulation of the environment.

Rhesus mother-infant pairs were housed in a playpen apparatus beginning just before the birth of four male infants. The infants were separated from their mothers four times beginning at a mean age of 218 days. In Type A separations (I and IV) the infants were removed and housed away from their familiar environment in a protected setting; in Type B separations (II and III) the infants remained in the familiar setting and mothers were removed. One pair was separated every 2 weeks for 6 days; for a particular infant, a mean of 8 weeks intervened between each of the separations. On the basis of infant behavior during separation. Type B separations appeared to have a more deleterious effect on the infant: infants did not show the typical behavioral signs of depression under Type A housing conditions, whereas, under Type B conditions, infants expressed the typical depressive reaction to separation. However, comparisons of pre- and postseparation behaviors in the mother-infant pairs indicated that Type A separations were more perturbing. Increases in ventral-ventral contact between mothers and infants were greater following Type A separations and increases in time at nipple occurred only after Type A separations; infant grooming by mother increased only after the first, a Type A, separation. Type B separations may have affected mothers more severely in that reciprocity between maternal cradling and infant clinging was greater following Type B separations than following Type A separations when infants clung significantly more often than mother cradled.

Animals↗
PubMed1978

Isolation and biological characterization of an adenovirus of rhesus macaques.

The etiology of a disease in rhesus monkeys the main clinical manifestation of which was acute conjunctivitis of an epizootic character has been studied. The cytopathogenic agent well propagating in primarily trypsinized kidney cells of monkeys has been isolated when investigating the affected eye mucosa. It was not pathogenic for laboratory animals. The mean diameter of the virions is 75 nm, the buoyant density in CsCl is 1.34 g/cm3, the viral DNA density is 1.706 g/cm3. The biological properties and findings of physicochemical, electron-microscopic, and serologic investigations allow one to allocate the isolated agent to the SV-37 strain, a representative of the adenovirus group.

Adenoviridae↗
PubMed1976

[Structural changes in the marker chromosome of rhesus macaques subjected to irradiation].

Using 48 Macaca rhesus undergone acute single does and prolonged small dose daily irradiation, a long-term preservation of reconstructions in the pair of marker nucleolus-forming chromosomes has been shown. The animals were examined in different periods from irradiation, ranging from 3 months to 16.5 years. The frequency of retained reconstructions in the long arms of chromosomes was reliably above the frequency of alterations in the short arms. Reconstructions in the long arms of the marker chromosome were seen in the heterochromatin area after differential chromosome staining. Alterations in the functionally active area of the short arms of the marker chromosome retained extremely rarely being observed only in monkeys that survived through long-term small-dose irradiation.

Animals↗
PubMed1978

[Cellular composition of the lymph nodes of monkeys (rhesus macaque) under normal and experimental conditions].

By means of mathematical methods, quantitative and qualitative changes were studied in different structural components of the mesenteric (ileocecal) lymph nodes in normal monkeys (Macaca rhesus) and under per os administration of Salmonella typhi murium, streptomycin-dependent. Cellular composition was calculated in the cortical plateau, cortical (lymphoid) cords and in follicules. Average percent of every cell type was determined. Vaccine administration, was stated to inhibit cytopoiesis in the cortical plateau and in the follicules with light centers. An inverse correlation was noted between the content of small and medium size lymphocytes. Different reactivity of certain structural components in the lymph nodes was demonstrated. As a response to the vaccine administration, plasmocellular acidophilic and macrophagal reactions were most pronounced in the cortical (lymphoid) cords.

Animals↗
PubMed1978

[Alteration of the construction and cellular composition of ileo-colonic lymph nodes of rhesus macaques after administration of salmonella vaccine].

In stained histological sections, percentage ratio of areas to different cellular elements in structural components of the ileocolonic lymph nodes was studied in mature Macaca rhesus, normal and after injection of salmonella vaccine. A rather considerable reaction in all structural components and cell composition of the lymph nodes was demonstrated as a response to immunization of the animals. These changes were demonstrated in decreased area occupied by the cortical substance and in increased area occupied by the medullar substance of the lymph node. In the cortical substance, together with decrease in the cortical plateau, total number of folliculi rises with formation of light centers in them. Calculation of cellular elements revealed that in the cortical substance cytopoietic function was inhibited; that was expressed in decreasing mitoses and blast forms in the cells. Most drastic alterations occur in myelin cords of the lymph nodes. Together with increasing area, a considerable reaction of acidophilic leucocytes, premature plasma cells and macrophages is observed. Their number increases notably.

Animals↗
PubMed2025

Proteomics and Phosphoproteomics Characteristics of the Rhesus Macaque Lung Infected With Original SARS-CoV-2, Delta, and Omicron Variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains mutate rapidly, making it crucial to study their molecular mechanisms for swift vaccine and drug development. Here, we utilized host lung proteomic and phosphoproteomic profiling to investigate the underlying pathology caused by the variants. Lung tissues infected with wild-type GD108, Delta, or Omicron BA.1 variants showed overexpression of proteins and phosphoproteins linked to the innate immune pathway, particularly in the Omicron group, with high activation of NOD-receptor and RIG-I like receptor signaling pathways. Protein-protein interaction (PPI) analysis revealed six key proteins, including antiviral innate immune response receptor RIG-I (DDX58), and five interferon-related proteins (IFIT2, ISG15, MX1, STAT1, and EIF2AK2), highlighting the importance of the innate immune response in combating all three variants. Kinase prediction analysis suggested that six kinases (DAPK1, DAPK2, DAPK3, PRACK, TTK, and MAP2K2), potentially inhibited by Fostamatinib, were activated across all three variants, and might be potential drug targets, pending further verification. Omicron infection, compared to other mutants, significantly disrupted proteins related to pulmonary structural support, like integrin and collagens, and inhibited efferocytosis, reducing the host's ability to eliminate the pathogen. These findings suggest that innate immune activation and structural disruption may contribute to Omicron-related pathology, potentially being useful for research into the molecular mechanisms underlying lung injury from SARS-CoV-2 variants.

Animals↗
PubMed1979

Breeding performance of a captive colony of rhesus macaques (Macaca mulatta).

For most of the 18 years recorded, fewer than 50% of the adult females gave birth in any one year. The colony, of 6 social groups, showed a clear-cut breeding season. Female parity and dominance had no effect on breeding rate, though 1st infants were born earlier in the year than 2nd-born ones. Only when females gave birth in successive years were the months of giving birth correlated. Mothers and daughters may tend to give birth closer in time within a breeding season than do other females.

Animal Feed↗
PubMed1977

Immunologic surface markers on nonhuman primate lymphocytes.

Peripheral blood lymphocytes from 37 healthy rhesus macaques (Macaca mulatta) and thymocytes from 10 fetal and neonatal rhesus macaques were studied for membrane characteristics. Spontaneous rosette formation with sheep erythrocytes, a characteristic of human T lymphocytes, was evaluated. The presence of membrane-bound immunoglobulin and surface receptors for fixed complement was measured, using fluorescent antibody techniques and erythrocyte-antibody-complement rosettes, respectively. The mean percentages +/- 1 standard error of the lymphocyte markers in the peripheral blood lymphocytes from the macaques were: spontaneous rosettes, 63 +/- 1.0; erythrocyte-antibody-complement rosettes, 14.9 +/- 1.2; and membrane immunoglobulin-positive cells, 21.9 +/- 2.2. These values are very similar to values reported for human beings.

Animals↗
PubMed2026

Adaptive and degenerative mitochondrial remodeling define distinct redox states in age-related macular degeneration.

Age-related macular degeneration (AMD) is associated with mitochondrial dysfunction and oxidative stress, yet the relationship between mitochondrial remodeling, redox homeostasis, and disease progression remains poorly understood. Nonhuman primates (NHPs) develop spontaneous AMD-related phenotypes, including punctate deposits and soft drusen, providing a unique animal model to investigate mitochondrial pathology in the aging retinal pigment epithelium (RPE). We integrated quantitative mitochondrial ultrastructural profiling with flavoprotein fluorescence imaging, plasma metabolomics, and whole-exome sequencing to characterize mitochondrial and redox alterations in aged rhesus macaques with AMD-related lesions. Flavoprotein fluorescence imaging demonstrated increased metabolic heterogeneity in eyes with soft drusen, consistent with altered mitochondrial redox states and oxidative stress. Morphometric analysis identified distinct mitochondrial remodeling patterns across phenotypes. Normal aging was characterized by concentric cristae and type I paracrystalline inclusions. Eyes with punctate deposits exhibited increased mitochondrial fusion-associated morphology, hyperbranching, and type I paracrystalline inclusions, consistent with a stress-responsive mitochondrial remodeling pattern. In contrast, eyes with soft drusen exhibited reduced fusion-associated morphology, reduced structural complexity, and ultrastructural features consistent with mitochondrial deterioration. These ultrastructural patterns were accompanied by distinct plasma metabolomic signatures. Punctate deposits were associated with altered glycolytic, tricarboxylic acid cycle, and redox-buffering metabolites, consistent with differences in stress-responsive metabolism, whereas soft drusen exhibited metabolomic signatures consistent with altered redox homeostasis. Whole-exome sequencing identified a mitochondrial DNA variant, MT:9582G > A, in cytochrome c oxidase subunit III (COX3) associated with the drusen phenotype. Collectively, these findings identify distinct mitochondrial remodeling patterns associated with AMD-related phenotypes in aged rhesus macaques. The convergence of ultrastructural, imaging, metabolomic, and genetic analyses suggests that punctate deposits and soft drusen are associated with different mitochondrial and redox-related responses to chronic retinal stress. These findings provide a framework for future studies investigating mitochondrial biology and redox-driven mechanisms in AMD.

Animals↗
PubMed1979

Immunofluorescent and immunoelectron microscopic demonstration of primate heart muscle antigens cross-reactive with Streptococcus pyogenes.

The presence of antigens in heart muscles cross-reactive with antibodies against Streptococcus pyogenes were examined in heart samples of seven primate species (chimpanzee, rhesus macaque, stump-tailed macaque, hamadryas baboon, capuchin monkey, green monkey and patas monkey). Cross-reactive antigens were localized by means of the indirect immunofluorescent technique in nearly all samples tested. The fluorescence pattern was the same as found in the heart muscle of other mammals. Using the indirect immunoferritin technique the substructural distribution of the antigens was investigated in heart muscle of rhesus macaque and hamadryas baboon. Beside the location on the cell surface the antigens were also demonstrated within the cell. Above all there was a strong labelling along the intercalated discs and in the sarcoplasmatic reticulum.

Animals↗