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1.
Physiol Rep ; 12(13): e16097, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38955666

ABSTRACT

Latent associations between low serum amylase and reduced plasma insulin levels and increased adiposity have been described previously in a small study of asymptomatic middle-aged humans. In the present study, we sought to determine the nature of such changes during the longitudinal progression from metabolically normal to overt type 2 diabetes mellitus (T2DM) in nonhuman primates (NHPs), a disease that appears to be the same in both pathophysiology and underlying mechanisms as that which most commonly develops in middle-aged adult humans. Amylase and lipase levels were characterized in 157 unrelated adult rhesus monkeys (Macaca mulatta); 38% developed T2DM while under study. In all monkeys, multivariable linear regression analysis revealed that amylase could be negatively predicted by % body fat (ß -0.29; p = 0.002), age (ß -0.27; p = 0.005), and HbA1c (ß -0.18; p = 0.037). Amylase levels were positively predicted by lipase levels (ß = 0.19; p = -0.024) in all NHPs included in the study. Amylase was significantly lower in NHPs with metabolic syndrome (p < 0.001), prediabetes (PreDM) (p < 0.001), and T2DM (p < 0.001) compared to metabolically normal adult NHPs. Lipase increased in NHPs with PreDM (p = 0.005) and T2DM (p = 0.04) compared to normal NHPs. This is the first longitudinal study of any species, including humans, to show the dynamics of amylase and lipase during the metabolic progression from normal to metabolic syndrome, to PreDM and then to overt T2DM. The extraordinary similarity between humans and monkeys in T2DM, in pancreatic pathophysiology and in metabolic functions give these findings high translational value.


Subject(s)
Amylases , Diabetes Mellitus, Type 2 , Lipase , Macaca mulatta , Metabolic Syndrome , Animals , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Lipase/blood , Lipase/metabolism , Male , Metabolic Syndrome/blood , Metabolic Syndrome/metabolism , Longitudinal Studies , Amylases/blood , Amylases/metabolism , Female
2.
Proc Natl Acad Sci U S A ; 121(29): e2316765121, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38990946

ABSTRACT

How does the brain simultaneously process signals that bring complementary information, like raw sensory signals and their transformed counterparts, without any disruptive interference? Contemporary research underscores the brain's adeptness in using decorrelated responses to reduce such interference. Both neurophysiological findings and artificial neural networks support the notion of orthogonal representation for signal differentiation and parallel processing. Yet, where, and how raw sensory signals are transformed into more abstract representations remains unclear. Using a temporal pattern discrimination task in trained monkeys, we revealed that the second somatosensory cortex (S2) efficiently segregates faithful and transformed neural responses into orthogonal subspaces. Importantly, S2 population encoding for transformed signals, but not for faithful ones, disappeared during a nondemanding version of this task, which suggests that signal transformation and their decoding from downstream areas are only active on-demand. A mechanistic computation model points to gain modulation as a possible biological mechanism for the observed context-dependent computation. Furthermore, individual neural activities that underlie the orthogonal population representations exhibited a continuum of responses, with no well-determined clusters. These findings advocate that the brain, while employing a continuum of heterogeneous neural responses, splits population signals into orthogonal subspaces in a context-dependent fashion to enhance robustness, performance, and improve coding efficiency.


Subject(s)
Macaca mulatta , Somatosensory Cortex , Animals , Somatosensory Cortex/physiology , Models, Neurological , Male
3.
Nat Commun ; 15(1): 5738, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982106

ABSTRACT

Natural behaviors occur in closed action-perception loops and are supported by dynamic and flexible beliefs abstracted away from our immediate sensory milieu. How this real-world flexibility is instantiated in neural circuits remains unknown. Here, we have male macaques navigate in a virtual environment by primarily leveraging sensory (optic flow) signals, or by more heavily relying on acquired internal models. We record single-unit spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and the dorso-lateral prefrontal cortex (dlPFC). Results show that while animals were able to maintain adaptive task-relevant beliefs regardless of sensory context, the fine-grain statistical dependencies between neurons, particularly in 7a and dlPFC, dynamically remapped with the changing computational demands. In dlPFC, but not 7a, destroying these statistical dependencies abolished the area's ability for cross-context decoding. Lastly, correlational analyses suggested that the more unit-to-unit couplings remapped in dlPFC, and the less they did so in MSTd, the less were population codes and behavior impacted by the loss of sensory evidence. We conclude that dynamic functional connectivity between neurons in prefrontal cortex maintain a stable population code and context-invariant beliefs during naturalistic behavior.


Subject(s)
Macaca mulatta , Neurons , Prefrontal Cortex , Animals , Male , Prefrontal Cortex/physiology , Neurons/physiology , Temporal Lobe/physiology , Parietal Lobe/physiology , Behavior, Animal/physiology
4.
J Med Primatol ; 53(4): e12722, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38949157

ABSTRACT

BACKGROUND: Tuberculosis (TB) kills approximately 1.6 million people yearly despite the fact anti-TB drugs are generally curative. Therefore, TB-case detection and monitoring of therapy, need a comprehensive approach. Automated radiological analysis, combined with clinical, microbiological, and immunological data, by machine learning (ML), can help achieve it. METHODS: Six rhesus macaques were experimentally inoculated with pathogenic Mycobacterium tuberculosis in the lung. Data, including Computed Tomography (CT), were collected at 0, 2, 4, 8, 12, 16, and 20 weeks. RESULTS: Our ML-based CT analysis (TB-Net) efficiently and accurately analyzed disease progression, performing better than standard deep learning model (LLM OpenAI's CLIP Vi4). TB-Net based results were more consistent than, and confirmed independently by, blinded manual disease scoring by two radiologists and exhibited strong correlations with blood biomarkers, TB-lesion volumes, and disease-signs during disease pathogenesis. CONCLUSION: The proposed approach is valuable in early disease detection, monitoring efficacy of therapy, and clinical decision making.


Subject(s)
Biomarkers , Deep Learning , Macaca mulatta , Mycobacterium tuberculosis , Tomography, X-Ray Computed , Animals , Biomarkers/blood , Tomography, X-Ray Computed/veterinary , Tuberculosis/veterinary , Tuberculosis/diagnostic imaging , Disease Models, Animal , Tuberculosis, Pulmonary/diagnostic imaging , Male , Female , Lung/diagnostic imaging , Lung/pathology , Lung/microbiology , Monkey Diseases/diagnostic imaging , Monkey Diseases/microbiology
5.
Proc Natl Acad Sci U S A ; 121(29): e2310421121, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38976733

ABSTRACT

We generated a replication-competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in place of the native spike (rOC43-CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2 S and SARS-CoV-2 by S-specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2 S. Single-dose immunization with rOC43-CoV2 S generates high levels of neutralizing antibodies against SARS-CoV-2 and fully protects human ACE2 transgenic mice from SARS-CoV-2 lethal challenge, despite nondetectable replication in respiratory and nonrespiratory organs. rOC43-CoV2 S induces S-specific serum and airway mucosal immunoglobulin A and IgG responses in rhesus macaques. rOC43-CoV2 S has enormous value as a BSL-2 agent to measure S-specific antibodies in the context of a bona fide CoV and is a candidate live attenuated SARS-CoV-2 mucosal vaccine that preferentially replicates in the upper airway.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Neutralization Tests , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Humans , Antibodies, Neutralizing/immunology , Mice , COVID-19/immunology , COVID-19/virology , COVID-19/prevention & control , Antibodies, Viral/immunology , Neutralization Tests/methods , Mice, Transgenic , Coronavirus OC43, Human/immunology , Coronavirus OC43, Human/genetics , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/immunology , Chlorocebus aethiops , Vero Cells , Macaca mulatta
6.
Elife ; 132024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968311

ABSTRACT

Object classification has been proposed as a principal objective of the primate ventral visual stream and has been used as an optimization target for deep neural network models (DNNs) of the visual system. However, visual brain areas represent many different types of information, and optimizing for classification of object identity alone does not constrain how other information may be encoded in visual representations. Information about different scene parameters may be discarded altogether ('invariance'), represented in non-interfering subspaces of population activity ('factorization') or encoded in an entangled fashion. In this work, we provide evidence that factorization is a normative principle of biological visual representations. In the monkey ventral visual hierarchy, we found that factorization of object pose and background information from object identity increased in higher-level regions and strongly contributed to improving object identity decoding performance. We then conducted a large-scale analysis of factorization of individual scene parameters - lighting, background, camera viewpoint, and object pose - in a diverse library of DNN models of the visual system. Models which best matched neural, fMRI, and behavioral data from both monkeys and humans across 12 datasets tended to be those which factorized scene parameters most strongly. Notably, invariance to these parameters was not as consistently associated with matches to neural and behavioral data, suggesting that maintaining non-class information in factorized activity subspaces is often preferred to dropping it altogether. Thus, we propose that factorization of visual scene information is a widely used strategy in brains and DNN models thereof.


When looking at a picture, we can quickly identify a recognizable object, such as an apple, applying a single word label to it. Although extensive neuroscience research has focused on how human and monkey brains achieve this recognition, our understanding of how the brain and brain-like computer models interpret other complex aspects of a visual scene ­ such as object position and environmental context ­ remains incomplete. In particular, it was not clear to what extent object recognition comes at the expense of other important scene details. For example, various aspects of the scene might be processed simultaneously. On the other hand, general object recognition may interfere with processing of such details. To investigate this, Lindsey and Issa analyzed 12 monkey and human brain datasets, as well as numerous computer models, to explore how different aspects of a scene are encoded in neurons and how these aspects are represented by computational models. The analysis revealed that preventing effective separation and retention of information about object pose and environmental context worsened object identification in monkey cortex neurons. In addition, the computer models that were the most brain-like could independently preserve the other scene details without interfering with object identification. The findings suggest that human and monkey high level ventral visual processing systems are capable of representing the environment in a more complex way than previously appreciated. In the future, studying more brain activity data could help to identify how rich the encoded information is and how it might support other functions like spatial navigation. This knowledge could help to build computational models that process the information in the same way, potentially improving their understanding of real-world scenes.


Subject(s)
Magnetic Resonance Imaging , Neural Networks, Computer , Animals , Humans , Male , Macaca mulatta/physiology , Visual Pathways/physiology , Visual Perception/physiology , Visual Cortex/physiology , Female , Photic Stimulation , Models, Neurological
7.
Cell Stem Cell ; 31(7): 941-943, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38971143

ABSTRACT

Induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) therapy has emerged as a highly promising field of heart repair. Lin et al.1 presented compelling evidence on the long-term engraftment and maturation of autologous iPSC-CMs in two rhesus macaques, demonstrating unprecedented cardiac autografting data in large animal models without the need of immunosuppressants.


Subject(s)
Induced Pluripotent Stem Cells , Macaca mulatta , Myocytes, Cardiac , Animals , Induced Pluripotent Stem Cells/cytology , Myocytes, Cardiac/cytology , Autografts , Humans , Cell Survival , Cell Differentiation
8.
Sci Rep ; 14(1): 15677, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977718

ABSTRACT

Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.


Subject(s)
Gastrointestinal Microbiome , Liver Cirrhosis , Macaca mulatta , Metagenomics , RNA, Ribosomal, 16S , Animals , Macaca mulatta/microbiology , Gastrointestinal Microbiome/genetics , Liver Cirrhosis/microbiology , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Male , RNA, Ribosomal, 16S/genetics , Metagenomics/methods , Feces/microbiology , Metagenome , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification
9.
Invest Ophthalmol Vis Sci ; 65(8): 22, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38995114

ABSTRACT

Purpose: To determine the relationship between visual sensitivities from white-on-white Goldmann size I to V stimuli and the underlying retinal ganglion cell (RGC) content in the non-human primate (NHP) experimental glaucoma model. Methods: Normative data were collected from 13 NHPs. Unilateral experimental glaucoma was induced in seven animals with the least variable fields who were monitored using optical coherence tomography and 30-2 full-threshold standard automated perimetry (SAP). At varying endpoints, animals were euthanized followed by perfusion fixation, and 1-mm retinal punches were obtained from 34 corresponding SAP locations. RGCs were immunolabeled with an antibody against an RNA-binding protein (RBPMS) marker and imaged using confocal microscopy. RGC counts from each location were then related to visual sensitivities for each stimulus size, after accounting for ocular magnification. Results: At the endpoint, the circumpapillary retinal nerve fiber layer thickness for experimental glaucoma eyes ranged from 47 to 113 µm. RGC density in control eyes was greatest for the 4.24° sample (18,024 ± 6869 cells/mm2) and decreased with eccentricity. Visual sensitivity at each tested location followed that predicted by spatial summation, with the critical area increasing with eccentricity (slope = 0.0036, R2 = 0.44). The relationship between RGC counts and visual sensitivity was described using a two-line fit, where the intercept of the first segment and hinge points were dependent on eccentricity. Conclusions: In NHPs, SAP visual thresholds are related to the underlying RGCs. The resulting spatial summation based structure-function model can be used to estimate RGC content from any standard white-on-white stimulus size.


Subject(s)
Disease Models, Animal , Glaucoma , Macaca mulatta , Retinal Ganglion Cells , Tomography, Optical Coherence , Visual Field Tests , Visual Fields , Animals , Retinal Ganglion Cells/pathology , Glaucoma/physiopathology , Glaucoma/diagnosis , Visual Field Tests/methods , Tomography, Optical Coherence/methods , Visual Fields/physiology , Male , Nerve Fibers/pathology , Intraocular Pressure/physiology , Female , Cell Count , Microscopy, Confocal
10.
Int J Mol Sci ; 25(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39000308

ABSTRACT

Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rhesus macaques infected with SHIV1157ipd3N4 for 5 years. One lineage of neutralizing antibodies (JT15 and JT16) targeted the V2-apex in the Env trimers, similar to the J038 lineage bnAbs identified in our previous study. The other lineage neutralizing antibody (JT18) targeted the V3 crown region in the Env, which strongly competed with human 447-52D. Each lineage antibody neutralized a different set of viruses. Interestingly, when the two neutralizing antibodies from different lineages isolated from the same macaque were combined, the mixture had a neutralization breath very similar to that from the cognate sera. Our study demonstrated that a minimum of two different neutralizing antibodies can fully recapitulate the serum neutralization breadth. This observation can have important implications in AIDS vaccine design.


Subject(s)
Antibodies, Neutralizing , HIV Antibodies , HIV-1 , Macaca mulatta , Simian Acquired Immunodeficiency Syndrome , Macaca mulatta/immunology , Animals , HIV-1/immunology , HIV Antibodies/immunology , HIV Antibodies/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Humans , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/blood , Simian Acquired Immunodeficiency Syndrome/virology , HIV Infections/immunology , HIV Infections/virology , HIV Infections/blood , Simian Immunodeficiency Virus/immunology , env Gene Products, Human Immunodeficiency Virus/immunology , Neutralization Tests
11.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(7): 696-705, 2024 Jul 09.
Article in Chinese | MEDLINE | ID: mdl-38949138

ABSTRACT

Objective: To investigate the presence of a distinct stem cell populations different from mesenchymal stem cells in the mandibular periosteum of both human and non-human primates (macaca mulatta), to explore its properties during intramembranous osteogenesis and to establish standard protocols for the isolation, culturing and expanding of mandibular periosteal stem cells (PSC) distinguished from other PSCs in other anatomical regions. Methods: Periosteum was harvested from the bone surface during flap bone removal in patients aged 18-24 years undergoing third molar extraction and from the buccal side of the mandibular premolar region of 6-year-old macaca mulatta respectively, and then subjected to single-cell sequencing using the Illumina platform Novaseq 6000 sequencer. Cross-species single-cell transcriptome sequencing results were compared using homologous gene matching. PSC were isolated from primary tissues using two digestion methods with body temperature and low temperature, and their surface markers (CD200, CD31, CD45 and CD90) were identified by cell flow cytometry. The ability of cell proliferation and three-lineage differentiation of PSC expanded to the third generation in vitro in different species were evaluated. Finally, the similarities and differences in osteogenic properties of PSC and bone marrow mesenchymal stem cells (BMSC) were compared. Results: The single-cell sequencing results indicated that 18 clusters of cell populations were identified after homologous gene matching for dimensionality reduction, and manual cellular annotation was conducted for each cluster based on cell marker databases. The comparison of different digestion protocols proved that the low-temperature overnight digestion protocol can stably isolate PSC from the human and m. mulatta mandibular periosteum and the cells exhibited a fibroblast-like morphology. This research confirmed that PSC of human and m. mulatta had similar proliferation capabilities through the cell counting kit-8 assay. Flow cytometry analysis was then used to identify the cells isolated from the periosteum expressed CD200(+), CD31(-), CD45(-), CD90(-). Then, human and m. mulatta PSC were induced into osteogenesis, adipogenesis, and chondrogenesis to demonstrate their corresponding multi-lineage differentiation capabilities. Finally, comparison with BMSC further clarified the oesteogenesis characteristics of PSC. The above experiments proved that the cells isolated from the periosteum were peiosteal cells with characteristics of stem cells evidenced by their cell morphology, proliferation ability, surface markers, and differentiation ability, and that this group of PSC possessed characteristics different from traditional mesenchymal stem cells. Conclusions: In this study, normal mandibular PSC from humans and m. mulatta were stably isolated and identified for the first time, providing a cellular foundation for investigating the mechanism of mandibular intramembranous osteogenesis, exploring ideal non-human primate models and establishing innovative strategies for clinically mandibular injury repair.


Subject(s)
Cell Differentiation , Macaca mulatta , Mandible , Periosteum , Single-Cell Analysis , Animals , Humans , Periosteum/cytology , Mandible/cytology , Osteogenesis , Stem Cells/cytology , Mesenchymal Stem Cells/cytology , Flow Cytometry , Young Adult , Adolescent , Cell Separation/methods
12.
PLoS Pathog ; 20(7): e1012339, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38950078

ABSTRACT

The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.


Subject(s)
COVID-19 , Immunologic Memory , Interleukin-10 , Macaca mulatta , Memory T Cells , SARS-CoV-2 , Animals , Interleukin-10/immunology , Interleukin-10/metabolism , COVID-19/immunology , SARS-CoV-2/immunology , Memory T Cells/immunology , Memory T Cells/metabolism , Immunologic Memory/immunology , Lung/immunology , Lung/virology , Lung/pathology , Disease Models, Animal , Interferon-gamma/metabolism , Interferon-gamma/immunology , T-Lymphocytes/immunology
13.
Nat Commun ; 15(1): 5369, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987235

ABSTRACT

Visual object memory is a fundamental element of various cognitive abilities, and the underlying neural mechanisms have been extensively examined especially in the anterior temporal cortex of primates. However, both macroscopic large-scale functional network in which this region is embedded and microscopic neuron-level dynamics of top-down regulation it receives for object memory remains elusive. Here, we identified the orbitofrontal node as a critical partner of the anterior temporal node for object memory by combining whole-brain functional imaging during rest and a short-term object memory task in male macaques. Focal chemogenetic silencing of the identified orbitofrontal node downregulated both the local orbitofrontal and remote anterior temporal nodes during the task, in association with deteriorated mnemonic, but not perceptual, performance. Furthermore, imaging-guided neuronal recordings in the same monkeys during the same task causally revealed that orbitofrontal top-down modulation enhanced stimulus-selective mnemonic signal in individual anterior temporal neurons while leaving bottom-up perceptual signal unchanged. Furthermore, similar activity difference was also observed between correct and mnemonic error trials before silencing, suggesting its behavioral relevance. These multifaceted but convergent results provide a multiscale causal understanding of dynamic top-down regulation of the anterior temporal cortex along the ventral fronto-temporal network underpinning short-term object memory in primates.


Subject(s)
Neurons , Temporal Lobe , Animals , Male , Temporal Lobe/physiology , Neurons/physiology , Macaca mulatta , Memory/physiology , Magnetic Resonance Imaging , Frontal Lobe/physiology , Memory, Short-Term/physiology , Brain Mapping , Prefrontal Cortex/physiology
14.
Xenotransplantation ; 31(4): e12873, 2024.
Article in English | MEDLINE | ID: mdl-38961605

ABSTRACT

BACKGROUND: Significant progress has been made in kidney xenotransplantation in the past few years, and this field is accelerating towards clinical translation. Therefore, surveillance of the xenograft with appropriate tools is of great importance. Ultrasonography has been widely used in kidney allotransplantation and served as an economical and non-invasive method to monitor the allograft. However, questions remain whether the ultrasonographic criteria established for human kidney allograft could also be applied in xenotransplantation. METHODS: In the current study, we established a porcine-rhesus life sustaining kidney xenotransplantation model. The xenograft underwent intensive surveillance using gray-scale, colorful Doppler ultrasound as well as 2D shear wave elastography. The kidney growth, blood perfusion, and cortical stiffness were measured twice a day. These parameters were compared with the clinical data including urine output, chemistry, and pathological findings. RESULTS: The observation continued for 16 days after transplantation. Decline of urine output and elevated serum creatinine were observed on POD9 and biopsy proven antibody-mediated rejection was seen on the same day. The xenograft underwent substantial growth, with the long axis length increased by 32% and the volume increased by threefold at the end of observation. The resistive index of the xenograft arteries elevated in response to rejection, together with impaired cortical perfusion, while the peak systolic velocity (PSV) was not compromised. The cortical stiffness also increased along with rejection. CONCLUSION: In summary, the ultrasound findings of kidney xenograft shared similarities with those in allograft but possessed some unique features. A modified criteria needs to be established for further application of ultrasound in kidney xenotransplantation.


Subject(s)
Graft Rejection , Heterografts , Kidney Transplantation , Kidney , Macaca mulatta , Transplantation, Heterologous , Animals , Transplantation, Heterologous/methods , Kidney Transplantation/methods , Swine , Kidney/diagnostic imaging , Humans , Ultrasonography/methods
15.
J Med Primatol ; 53(4): e12724, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39014527

ABSTRACT

In this report, we describe the gross, histopathology, and immunohistochemical findings of a thyroblastoma that arose in the right lobe of the thyroid gland in a 2-month-old rhesus macaque (Macaca mulatta).


Subject(s)
Macaca mulatta , Monkey Diseases , Thyroid Neoplasms , Animals , Monkey Diseases/pathology , Monkey Diseases/diagnosis , Thyroid Neoplasms/veterinary , Thyroid Neoplasms/pathology , Thyroid Neoplasms/diagnosis , Male , Female
16.
Nat Commun ; 15(1): 5658, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969634

ABSTRACT

Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.


Subject(s)
Disease Models, Animal , Genetic Variation , Macaca mulatta , Animals , Macaca mulatta/genetics , Humans , Gene Frequency , Optic Atrophy, Autosomal Dominant/genetics , Polymorphism, Single Nucleotide , Phenotype , Machine Learning , Genotype , Mutation, Missense
17.
Proc Biol Sci ; 291(2027): 20240984, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39013427

ABSTRACT

Social living affords primates (including humans) many benefits. Communication has been proposed to be the key mechanism used to bond social connections, which could explain why primates have evolved such expressive faces. We assessed whether the facial expressivity of the dominant male (quantified from the coding of anatomically based facial movement) was related to social network properties (based on social proximity and grooming) in nine groups of captive rhesus macaques (Macaca mulatta) housed in uniform physical and social environments. More facially expressive dominant male macaques were more socially connected and had more cohesive social groups. These findings show that inter-individual differences in facial expressivity are related to differential social outcomes at both an individual and group level. More expressive individuals occupy more beneficial social positions, which could help explain the selection for complex facial communication in primates.


Subject(s)
Facial Expression , Macaca mulatta , Animals , Macaca mulatta/physiology , Male , Social Dominance , Social Behavior , Grooming
18.
Nat Commun ; 15(1): 5963, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013855

ABSTRACT

While the hippocampus is key for human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro- and micro-structure, which shows anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species followed an anterior-posterior axis, we observed a marked reconfiguration in the latter across species, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Here we show that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding within heteromodal association networks.


Subject(s)
Biological Evolution , Hippocampus , Animals , Hippocampus/physiology , Hippocampus/anatomy & histology , Hippocampus/diagnostic imaging , Humans , Male , Female , Macaca , Magnetic Resonance Imaging/methods , Primates/physiology , Primates/anatomy & histology , Adult , Nerve Net/physiology , Nerve Net/diagnostic imaging , Nerve Net/anatomy & histology , Cerebral Cortex/physiology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/anatomy & histology , Neural Pathways/physiology , Neural Pathways/anatomy & histology , Macaca mulatta
19.
Nat Commun ; 15(1): 5861, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997274

ABSTRACT

Electrical stimulation is a key tool in neuroscience, both in brain mapping studies and in many therapeutic applications such as cochlear, vestibular, and retinal neural implants. Due to safety considerations, stimulation is restricted to short biphasic pulses. Despite decades of research and development, neural implants lead to varying restoration of function in patients. In this study, we use computational modeling to provide an explanation for how pulsatile stimulation affects axonal channels and therefore leads to variability in restoration of neural responses. The phenomenological explanation is transformed into equations that predict induced firing rate as a function of pulse rate, pulse amplitude, and spontaneous firing rate. We show that these equations predict simulated responses to pulsatile stimulation with a variety of parameters as well as several features of experimentally recorded primate vestibular afferent responses to pulsatile stimulation. We then discuss the implications of these effects for improving clinical stimulation paradigms and electrical stimulation-based experiments.


Subject(s)
Electric Stimulation , Animals , Electric Stimulation/methods , Models, Neurological , Macaca mulatta , Action Potentials/physiology , Neurons/physiology , Computer Simulation , Humans , Vestibule, Labyrinth/physiology
20.
Immun Inflamm Dis ; 12(6): e1318, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923761

ABSTRACT

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.


Subject(s)
HLA-DR Antigens , Histocompatibility Antigens Class II , T-Lymphocytes , Animals , Histocompatibility Antigens Class II/immunology , HLA-DR Antigens/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Humans , Macaca mulatta , Antibodies, Monoclonal/immunology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Saimiri/immunology , Callithrix/immunology , Flow Cytometry , Papio anubis/immunology , Platyrrhini/immunology
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