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Affective touch-a slow, gentle, and pleasant form of touch-activates a different neural network than which is activated during discriminative touch in humans. Affective touch perception is enabled by specialized low-threshold mechanoreceptors in the skin with unmyelinated fibers called C tactile (CT) afferents. These CT afferents are conserved across mammalian species, including macaque monkeys. However, it is unknown whether the neural representation of affective touch is the same across species and whether affective touch's capacity to activate the hubs of the brain that compute socioaffective information requires conscious perception. Here, we used functional MRI to assess the preferential activation of neural hubs by slow (affective) vs. fast (discriminative) touch in anesthetized rhesus monkeys (Macaca mulatta). The insula, anterior cingulate cortex (ACC), amygdala, and secondary somatosensory cortex were all significantly more active during slow touch relative to fast touch, suggesting homologous activation of the interoceptive-allostatic network across primate species during affective touch. Further, we found that neural responses to affective vs. discriminative touch in the insula and ACC (the primary cortical hubs for interoceptive processing) changed significantly with age. Insula and ACC in younger animals differentiated between slow and fast touch, while activity was comparable between conditions for aged monkeys (equivalent to >70 y in humans). These results, together with prior studies establishing conserved peripheral nervous system mechanisms of affective touch transduction, suggest that neural responses to affective touch are evolutionarily conserved in monkeys, significantly impacted in old age, and do not necessitate conscious experience of touch.

Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of social impairment in low-social monkeys and children with autism, suggesting that AVP administration may improve primate social functioning. However, AVP administration also increases aggression, at least in "neurotypical" animals with intact AVP signaling. Here, we tested the effects of a voluntary drug administration method in low-social male rhesus monkeys with high autistic-like trait burden. Monkeys received nebulized AVP or placebo, using a within-subjects design. Study 1 (N = 8) investigated the effects of AVP administration on social cognition in two tests comparing responses to social versus nonsocial stimuli. Test 1: Placebo-administered monkeys lacked face recognition memory, whereas face recognition memory was "rescued" following AVP administration. In contrast, object recognition memory was intact and did not differ between administration conditions. Test 2: Placebo-administered monkeys did not respond to conspecific social communication cues, whereas following AVP administration, they reciprocated affiliative communication cues with species-typical affiliative responses. Importantly, AVP administration did not increase aggressive responses to conspecific aggressive or affiliative overtures. Study 2 (N = 4) evaluated the pharmacokinetics of this administration method. Following AVP nebulization, we observed a linear increase in cisternal CSF AVP levels, and a quadratic rise and fall in blood AVP levels. These findings indicate that nebulized AVP likely penetrates the central nervous system, selectively promotes species-typical responses to social information, and does not induce aggression in low-social individuals. Nebulized AVP therefore may hold promise for managing similar social symptoms in people with autism, particularly in very young or lower functioning individuals. [ABSTRACT FROM AUTHOR]

In real-world vision, objects may appear for a short period, such as in conjunction with visual search. Presumably, this puts a premium on rapid categorization. We designed a visual categorization task cued by briefly presented images to study how visual categorization is processed in an ethologically relevant context. We compared the performance of monkeys with bilateral area TE lesions, and those with bilateral rhinal cortex lesions, to control animals. TE lesions impaired the accuracy but not the speed of visual categorization. In contrast, rhinal cortex lesions did not affect the accuracy but reduced the speed of visual categorization. A generalized drift-diffusion model (GDDM) with collapsing bounds was fitted to the data. The drift rate was equivalent across all groups, but the decision bounds collapsed more slowly in the rhinal group than in the other two groups. This suggests that, although evidence is accumulated at the same rate in all groups, the rhinal lesion results in slower decision-making. [ABSTRACT FROM AUTHOR]

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Objective To discuss the perioperative care and wound protection of xenotransplantation from genetically edited pigs to monkeys, with the goal of improving the success rate of such experimental procedures. Methods From October 2022 to October 2023, perioperative care and wound protection were performed on 7 recipient rhesus monkeys undergoing xenotransplantation of genetically edited pig tissues and organs. Customized wound protective garments were designed based on monkeys' size and surgical area to protect the wounds, alongside meticulous perioperative care. This included preoperative preparation and medication, intraoperative monitoring of physiological indicators and anesthesia management, and postoperative care comprising wound protection, observation and monitoring, and nutritional support. Results All seven monkeys successfully underwent xenotransplantation. With the aid of protective garments and detailed care, all surgical wounds healed by first intention, and postoperative recovery was satisfactory. Conclusion Proper care and wound protection during xenotransplantation from genetically edited pigs to monkeys not only promote wound healing, but also alleviate pain and harm to animals. This has significant implications for advancing experimental research in pig-monkey xenotransplantation and enhancing animal welfare. [ABSTRACT FROM AUTHOR]

Genome editing has the potential to treat genetic diseases in a variety of tissues, including the lung. We have previously developed and validated a dual adeno-associated virus (AAV) CRISPR platform that supports effective editing in the airways of mice. To validate this delivery vehicle in a large animal model, we have shown that intratracheal instillation of CRISPR/Cas9 in AAV5 can edit a housekeeping gene or a disease-related gene in the lungs of young rhesus monkeys. We observed up to 8% editing of angiotensin-converting enzyme 2 (ACE2) in lung lobes after single-dose administration. Single-nuclear RNA sequencing revealed that AAV5 transduces multiple cell types in the caudal lung lobes, including alveolar cells, macrophages, fibroblasts, endothelial cells, and B cells. These results demonstrate that AAV5 is efficient in the delivery of CRISPR/Cas9 in the lung lobes of young rhesus monkeys. [ABSTRACT FROM AUTHOR]

Aged rhesus monkeys, like aged humans, show declines in cognitive function. We present cognitive test data from a large sample of male and female rhesus monkeys, 34 young (aged 3.5-13.6 years) and 71 aged (aged 19.9-32.5 years at the start of cognitive testing). Monkeys were tested on spatiotemporal working memory (delayed response), visual recognition memory (delayed nonmatching to sample), and stimulus-reward association learning (object discrimination), tasks with an extensive evidence base in nonhuman primate neuropsychology. On average, aged monkeys performed worse than young on all 3 tasks. Acquisition of delayed response and delayed nonmatching to sample was more variable in aged monkeys than in young. Performance scores on delayed nonmatching to sample and object discrimination were associated with each other, but neither was associated with performance on delayed response. Sex and chronological age were not reliable predictors of individual differences in cognitive outcome among the aged monkeys. These data establish population norms for multiple cognitive tests in young and aged rhesus monkeys in the largest sample reported to date. They also illustrate independence of cognitive aging in task domains dependent on the prefrontal cortex and medial temporal lobe.

Abstract Background Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. Methods In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. Results We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. Conclusions This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

The rhesus monkey (Macaca mulatta) is one of the most frequently used primate species in biomedical research. As a common animal model used to study human disease, the validation of the obtained research data depends on a solid understanding of rhesus monkey anatomy. Unfortunately, the number of anatomical studies on the rhesus monkey is low. Moreover, the available anatomical books and atlases are outdated. For example, no color photographs—only line drawings—are presented. Luckily, renewed interest in rhesus monkey anatomy has been observed. The present study builds upon a recently published manuscript on the topographical anatomy of the thoracic limb of the rhesus monkey. More specifically, the musculature of the rhesus monkey hand is described using full-color anatomical photographs taken during dissections of the hands of three rhesus monkeys. The structures that are visible in the different layers, from the superficial to the deepest layer, are described using veterinary anatomical nomenclature. As expected, the anatomy of the rhesus monkey hand largely parallels human anatomy, which supports the value of the rhesus monkey as animal model. However, some remarkable differences have been identified as well. The present publication could therefore be useful when modeling the human hand (e.g., surgical protocols) using the rhesus monkey.

Background: Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. Methods: In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. Results: We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. Conclusions: This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp. [ABSTRACT FROM AUTHOR]

Shigellosis remains a significant global health challenge, particularly in Asia and Africa, where it is a major cause of morbidity and mortality among children. Despite the urgent need, the development of a licensed Shigella vaccine has been hindered, partly due to the lack of suitable animal models for preclinical evaluation. In this study, we used an intragastric adult rhesusmacaque challenge model to evaluate the safety, immunogenicity, and efficacy of five live-attenuated Shigella dysenteriae 1 vaccine candidates, all derived fromthe 1617 parent strain. The vaccine strains includedWRSd1, a previously tested candidate with deletions in virG(icsA), stxAB, and fnr, and four other strains--WRSd2, WRSd3, WRSd4, and WRSd5--each containing deletions in virG and stxAB, but retaining fnr. Additionally, WRSd3 and WRSd5 had further deletions in the Shigella enterotoxin gene senA and its paralog senB, with WRSd5 having an extra deletion in msbB2. Rhesus monkeys were immunized three times at two-day intervals with a target dose of 2 × 1010 CFU of the vaccine strains. Thirty days after the final immunization, all monkeys were challenged with a target dose of 2 × 109 CFU of the S. dysenteriae 1 1617 wild-type strain. Safety, immunogenicity, and efficacy were assessed through physical monitoring and the evaluation of immunologic and inflammatory markers following immunization and challenge. Initial doses of WRSd1, WRSd3, and WRSd5 led to mild adverse effects, such as vomiting and loose stools, but all five vaccine strains were well tolerated in subsequent doses. All strains elicited significant IgA and IgG antibody responses, as well as the production of antibody-secreting cells. Notably, none of the vaccinated animals exhibited shigellosis symptoms such as vomiting or loose/watery stool post-challenge, in stark contrast to the control group, where 39% and 61% of monkeys exhibited these symptoms, respectively. The aggregate clinical score used to evaluate Shigella attack rates post-challenge revealed a 72% attack rate in control animals, compared to only 13% in vaccinated animals, indicating a relative risk reduction of 81%. This study highlights the potential of this NHP model in evaluating the safety, immunogenicity, and efficacy of live-attenuated Shigella vaccine candidates, offering a valuable tool for preclinical assessment before advancing to Phase 1 or more advanced clinical trials. [ABSTRACT FROM AUTHOR]

In this novel large-scale multiplexed immunofluorescence study we comprehensively characterized and compared layer-specific proteomic features within regions of interest of the widely divergent dorsolateral prefrontal cortex (A46) and primary visual cortex (A17) of adult rhesus monkeys. Twenty-eight markers were imaged in rounds of sequential staining, and their spatial distribution precisely quantified within gray matter layers and superficial white matter. Cells were classified as neurons, astrocytes, oligodendrocytes, microglia, or endothelial cells. The distribution of fibers and blood vessels were assessed by quantification of staining intensity across regions of interest. This method revealed multivariate similarities and differences between layers and areas. Protein expression in neurons was the strongest determinant of both laminar and regional differences, whereas protein expression in glia was more important for intra-areal laminar distinctions. Among specific results, we observed a lower glia-to-neuron ratio in A17 than in A46 and the pan-neuronal markers HuD and NeuN were differentially distributed in both brain areas with a lower intensity of NeuN in layers 4 and 5 of A17 compared to A46 and other A17 layers. Astrocytes and oligodendrocytes exhibited distinct marker-specific laminar distributions that differed between regions; notably, there was a high proportion of ALDH1L1-expressing astrocytes and of oligodendrocyte markers in layer 4 of A17. The many nuanced differences in protein expression between layers and regions observed here highlight the need for direct assessment of proteins, in addition to RNA expression, and set the stage for future protein-focused studies of these and other brain regions in normal and pathological conditions. [ABSTRACT FROM AUTHOR]

The rhesus monkey (Macaca mulatta) is one of the most frequently used primate species in biomedical research. As a common animal model used to study human disease, the validation of the obtained research data depends on a solid understanding of rhesus monkey anatomy. Unfortunately, the number of anatomical studies on the rhesus monkey is low. Moreover, the available anatomical books and atlases are outdated. For example, no color photographs—only line drawings—are presented. Luckily, renewed interest in rhesus monkey anatomy has been observed. The present study builds upon a recently published manuscript on the topographical anatomy of the thoracic limb of the rhesus monkey. More specifically, the musculature of the rhesus monkey hand is described using full-color anatomical photographs taken during dissections of the hands of three rhesus monkeys. The structures that are visible in the different layers, from the superficial to the deepest layer, are described using veterinary anatomical nomenclature. As expected, the anatomy of the rhesus monkey hand largely parallels human anatomy, which supports the value of the rhesus monkey as animal model. However, some remarkable differences have been identified as well. The present publication could therefore be useful when modeling the human hand (e.g., surgical protocols) using the rhesus monkey. [ABSTRACT FROM AUTHOR]

In the development of drugs that affect the central nervous system (CNS), it is important to determine whether they have dependence potential and if so, to establish an effective dose within a range that does not manifest dependency. Methods for evaluating drug dependence include selfadministration tests using experimental animals while assessment of the minimum effective dose (MED) involves gross behavioral observation. This study aims to examine the relationship between the most frequently self-administered dose (peak self-administered dose, PSAD) and the MED amongst different types of CNS depressants in order to optimize dose range selection for the evaluation of drug reinforcing effects. PSAD was investigated by intravenous self-administration in rhesus monkeys conducted as daily 2 hr-sessions under a fixed ratio 5 schedule with a 1-min time-out after each administration. MED was investigated by gross behavioral observation following cumulative dosing. For opiates, the PSAD was 0.016 mg/kg/infusion for morphine, 0.06 mg/kg/infusion for codeine, 0.25 mg/kg/infusion for butorphanol and 0.063 mg/kg/infusion for pentazocine. For anesthetics and sedatives, the PSAD was 0.5 mg/kg/infusion for pentobarbital, 0.25 mg/kg/infusion for thiopental, 0.06 mg/kg/infusion for ketamine and 0.063 mg/kg/infusion for midazolam. The PSAD/MED ratio was 1/63-1/32 for opiates and 1/8-1/2 for anesthetics and hypnosedatives. While previous research by Fujiwara et al. (2016) suggested that a dose range lower than the MED for gross behavioral effects should be used for intravenous self-administration in the evaluation of drug reinforcing effects, this study further indicates that the optimal dose range may vary depending on drug type. [ABSTRACT FROM AUTHOR]

A thorough characterization of induced pluripotent stem cells (iPSCs) used with in vitro models or therapeutics is essential. Even iPSCs derived from a single donor can exhibit variability within and between cell lines, which can lead to heterogeneity in results and hinder the promising future of cell replacement therapies. In this study, the cell seeding density of human and rhesus monkey iPSCs was tested to maximize the cell line-specific yield of the generated cardiomyocytes. We found that, despite using the same iPSC generation and differentiation protocols, the cell seeding density for the cell line-specific best differentiation efficiency could differ by a factor of four for the four cell lines used here. In addition, the cell lines showed differences in the range of cell seeding densities that they could tolerate without the severe loss of differentiation efficiency. Overall, our data show that the cell seeding density is a critical parameter for the differentiation inefficiency of primate iPSCs to cardiomyocytes and that iPSCs generated with the same episomal approach still exhibit considerable heterogeneity. Therefore, individual characterization of iPSC lines is required, and functional comparability with in vivo processes must be ensured to warrant the translatability of in vitro research with iPSCs. [ABSTRACT FROM AUTHOR]

In real-world vision, objects may appear for a short period, such as in conjunction with visual search. Presumably, this puts a premium on rapid categorization. We designed a visual categorization task cued by briefly presented images to study how visual categorization is processed in an ethologically relevant context. We compared the performance of monkeys with bilateral area TE lesions, and those with bilateral rhinal cortex lesions, to control animals. TE lesions impaired the accuracy but not the speed of visual categorization. In contrast, rhinal cortex lesions did not affect the accuracy but reduced the speed of visual categorization. A generalized drift-diffusion model (GDDM) with collapsing bounds was fitted to the data. The drift rate was equivalent across all groups, but the decision bounds collapsed more slowly in the rhinal group than in the other two groups. This suggests that, although evidence is accumulated at the same rate in all groups, the rhinal lesion results in slower decision-making.

Accumulating evidence indicates that the adult brain is capable of significant structural change following damage-a capacity once thought to be largely limited to developing brains. To date, most existing research on adult plasticity has focused on how exteroceptive sensorimotor networks compensate for damage to preserve function. Interoceptive networks-those that represent and process sensory information about the body's internal state-are now recognized to be critical for a wide range of physiological and psychological functions from basic energy regulation to maintaining a sense of self, but the extent to which these networks remain plastic in adulthood has not been established. In this report, we used detailed histological analyses to pinpoint precise changes to gray matter volume in the interoceptive-allostatic network in adult rhesus monkeys (Macaca mulatta) who received neurotoxic lesions of the anterior cingulate cortex (ACC) and neurologically intact control monkeys. Relative to controls, monkeys with ACC lesions had significant and selective unilateral expansion of the ventral anterior insula and significant relative bilateral expansion of the lateral nucleus of the amygdala. This work demonstrates the capacity for neuroplasticity in the interoceptive-allostatic network which, given that changes included expansion rather than atrophy, is likely to represent an adaptive response following damage.

Study on food preference of Rhesus monkey (Macaca mulatta) was conducted from September 2019 to September 2020 in the Margalla Hills National Park (MHNP) near Islamabad, which falls in Murree foothills between 450m--1500m elevation (N 330 44'25.5" E 0730 03'15.3"). Topography is rugged and the climate is sub-tropical semi-arid. The flora of the park is mainly subtropical evergreen scrub forest on the lower slopes and subtropical pine forest at higher elevations. The data were collected by direct field observations on five selected groups: A, B, C, D and E of rhesus monkey in various parts of the study area. Food remnants method was used in combination with fecal analysis and visual observation for food composition. Both macroscopic and microscopic fecal analysis were carried out using 150 fecal pellets, collected from study area. The microhistological fecal analysis showed the presence of 29 dietary plant species as compared to 30 plant species observed in the field. No animal derived food component was noticed in the diet. The results revealed that food composition consisted of 83% plants diet, 14% provisioned food items and 03% scavenging on garbage bins. To study food resource preference, the monkeys were classified into five age/sex classes: Adult males, adult females, sub adults, juveniles and infants. Analysis of food resources preference of five age/sex classes of rhesus monkeys revealed that it mainly varied due to nutritional requirements and physiological conditions of monkeys. Rhesus monkeys preferred succulent foods to the non-succulents. Eight different feeding categories: arboreal, ground, provisioning, scavenging, begging, stealing, snatching and suckling were defined. A total of 540 observations were taken for all age and sex classes. The arboreal and ground feeding were widely used by the monkeys while stealing and snatching were little used. There is a need to conduct research on feeding ecology, parasitology, food preference based on nutritional requirements of Rhesus monkey in MHNP. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Morganella morganii (M. morganii) is a Gram-negative rod-shaped bacterium capable of infecting various animals including humans, pigs (Sus), European medical leeches (Hirudo medicinalis), bullfrogs (Rana catebeiana), south China tigers (Panthera tigris Amoyensis), guinea pigs (Cavia porcellus), and rabbits (Leporidae) and is responsible for causing diseases such as cellulitis, abscesses, sepsis, diarrhea, and bacteremia. Rhesus monkeys (Macaca mulatta) are indispensable experimental animals in biomedical research. Infection with M. morganii leads to severe clinical abnormalities that can potentially interfere with experimental outcomes. We successfully isolated and identified M. morganii from the uterine secretions of rhesus monkey in China. Furthermore, we determined its phylogenetic relationship and conducted drug sensitivity tests. A bacterium was isolated and identified from the secretion of a rhesus monkey with endometritis. The morphological results showed that the strain exhibited round, convex, gray-white colonies with smooth surfaces and diameters ranging from 1 to 2 mm when cultured on Columbia blood agar at 37 °C for 24 h; on salmonella–shigella agar (S.S.) at 37 °C for 24 h, the colonies appeared round, flat, and translucent. Gram staining showed negative results with blunt ends and non-spore-forming characteristics. Molecular biology results showed that the 16S rRNA sequence of the strain revealed over 96.9% similarity with published sequences of M. morganii from different sources in the NCBI GenBank database. Morphological and molecular biology analysis confirmed that the strain (RM2023) isolated from cervical secretions of rhesus monkey was M. morganii. Drug sensitivity testing demonstrated that the isolated strain (RM2023) was sensitive to ceftriaxone, amikacin, gentamicin, cefazolin, cefuroxime, ceftazidime, levofloxacin, cotrimoxazole, norfloxacin, and tetracycline; moderately sensitive to ampicillin; and resistant to penicillin, vancomycin, ciprofloxacin, and clindamycin. The research findings provide valuable insights for disease prevention in rhesus monkeys and contribute to molecular epidemiological studies. [ABSTRACT FROM AUTHOR]

Coxsackievirus B3 (CVB3) is the pathogen causing hand, foot and mouth disease (HFMD), which manifests across a spectrum of clinical severity from mild to severe. However, CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis, failing to replicate human HFMD symptoms. Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys, there is no comprehensive data on CVB3. In this study, we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes. The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip, leading to nasopharyngeal colonization, acute severe pathological injury, and typical HFMD symptoms. Notably, the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage. In the subsequent study, rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms, viral excretion, serum antibody conversion, viral nucleic acids and antigens, and the specific organ damages, particularly in the heart. Surprisingly, there were no significant differences in myocardial enzyme levels, and the clinical symptoms resembled those often associated with common, mild infections. In summary, the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD. These models could serve as a basis for understanding the disease pathogenesis, conducting pre-trial prevention and evaluation, and implementing post-exposure intervention. [ABSTRACT FROM AUTHOR]

Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First, we built a multicompartment pyramidal neuron model fit to monkey dlPFC empirical data, with an axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions. This model was used to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination. Next, we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from ultrastructure up to behavior during normal aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.

Late adolescence is a period of dynamic change in the brain as humans learn to navigate increasingly complex environments. In particular, prefrontal cortical (PFC) regions undergo extensive remodeling as the brain is fine-tuned to orchestrate cognitive control over attention, reasoning, and emotions. Late adolescence also presents a uniquely vulnerable period as neurodevelopmental illnesses, such as schizophrenia, become evident and worsen into young adulthood. Challenges in early development, including prenatal exposure to infection, may set the stage for a cascade of maladaptive events that ultimately result in aberrant PFC connectivity and function before symptoms emerge. A growing body of research suggests that activation of the mother's immune system during pregnancy may act as a disease primer, in combination with other environmental and genetic factors, contributing to an increased risk of neurodevelopmental disorders, including schizophrenia. Animal models provide an invaluable opportunity to examine the course of brain and behavioral changes in offspring exposed to maternal immune activation (MIA). Although the vast majority of MIA research has been carried out in rodents, here we highlight the translational utility of the nonhuman primate (NHP) as a model species more closely related to humans in PFC structure and function. In this review, we consider the protracted period of brain and behavioral maturation in the NHP, describe emerging findings from MIA NHP offspring in the context of rodent preclinical models, and lastly explore the translational relevance of the NHP MIA model to expand understanding of the etiology and developmental course of PFC pathology in schizophrenia.

Nonhuman primates are essential for the study of human disease and to explore the safety of new diagnostics and therapies proposed for human use. They share similar genetic, physiologic, immunologic, reproductive, and developmental features with humans and thus have proven crucial for the study of embryonic/fetal development, organ system ontogeny, and the role of the maternal-placental-fetal interface in health and disease. The fetus may be exposed to a variety of inflammatory stimuli including infectious microbes as well as maternal inflammation, which can result from infections, obesity, or environmental exposures. Growing evidence supports that inflammation is a mediator of fetal programming and that the maternal immune system is tightly integrated with fetal-placental immune responses that may set a postnatal path for future health or disease. This review addresses some of the unique features of the nonhuman primate model system, specifically the rhesus monkey (Macaca mulatta), and importance of the species for studies focused on organ system ontogeny and the impact of viral teratogens in relation to development and congenital disorders.

The sensation of internal bodily signals, such as when your stomach is contracting or your heart is beating, plays a critical role in broad biological and psychological functions ranging from homeostasis to emotional experience and self-awareness. The evolutionary origins of this capacity and, thus, the extent to which it is present in nonhuman animals remain unclear. Here, we show that rhesus monkeys (Macaca mulatta) spend significantly more time viewing stimuli presented asynchronously, as compared to synchronously, with their heartbeats. This is consistent with evidence previously shown in human infants using a nearly identical experimental paradigm, suggesting that rhesus monkeys have a human-like capacity to integrate interoceptive signals from the heart with exteroceptive audiovisual information. As no prior work has demonstrated behavioral evidence of innate cardiac interoceptive ability in nonhuman animals, these results have important implications for our understanding of the evolution of this ability and for establishing rhesus monkeys as an animal model for human interoceptive function and dysfunction. We anticipate that this work may also provide an important model for future psychiatric research, as disordered interoceptive processing is implicated in a wide variety of psychiatric conditions.

Decades of research studying the behavioral effects of damage to structures in medial temporal lobe of rhesus monkeys have documented that such damage, particularly damage to the amygdala, causes animals to become hyporesponsive to threat and hyper-social. This phenotype, a subset of the behaviors known as "Klüver-Bucy Syndrome," is one of the most well-known phenomena in behavioral neuroscience. Carrying on the tradition of evaluating hyposensitivity to threat in monkeys with temporal lobe lesions, we evaluated the responses of rhesus monkeys with bilateral ibotenic acid lesions of the amygdala or hippocampus and procedure-matched control animals to the presentation of an unfamiliar human intruder and threatening objects of varying complexity. All animals behaved as expected-calibrating their responses to the ostensible threat value of the stimuli such that they were most responsive to the most potent stimuli and least responsive to the least potent stimuli. Contrary to an earlier report (Mason et al., 2006), lesion status did not impact the pattern of responses across multiple dependent measures (overt behaviors, position in cage, etc.). The only lesion induced difference consistent with hyposensitivity to threat was that monkeys with amygdala lesions retrieved food rewards placed near reptile-like objects more rapidly than did control animals. These findings call into question the assumption that amygdala damage causes robust, stereotyped changes to affective behavior. They also highlight the importance of replication in neuroscientific studies using nonhuman primates. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Human epidemiological studies implicate exposure to infection during gestation in the etiology of neurodevelopmental disorders. Animal models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant offspring brain and behavior development. Here we evaluate neurodevelopment of male rhesus monkeys (Macaca mulatta) born to MIA-treated dams (n = 14) injected with a modified form of the viral mimic polyinosinic:polycytidylic acid at the end of the first trimester. Control dams received saline injections at the same gestational time points (n = 10) or were untreated (n = 4). MIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature, and inflammatory cytokines. Although offspring born to control or MIA-treated dams did not differ on measures of physical growth and early developmental milestones, the MIA-treated animals exhibited subtle changes in cognitive development and deviated from species-typical brain growth trajectories. Longitudinal MRI revealed significant gray matter volume reductions in the prefrontal and frontal cortices of MIA-treated offspring at 6 months that persisted through the final time point at 45 months along with smaller frontal white matter volumes in MIA-treated animals at 36 and 45 months. These findings provide the first evidence of early postnatal changes in brain development in MIA-exposed nonhuman primates and establish a translationally relevant model system to explore the neurodevelopmental trajectory of risk associated with prenatal immune challenge from birth through late adolescence.SIGNIFICANCE STATEMENT Women exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental disorder. Preclinical maternal immune activation (MIA) models have demonstrated that the effects of maternal infection on fetal brain development are mediated by maternal immune response. Since the majority of MIA models are conducted in rodents, the nonhuman primate provides a unique system to evaluate the MIA hypothesis in a species closely related to humans. Here we report the first longitudinal study conducted in a nonhuman primate MIA model. MIA-exposed offspring demonstrate subtle changes in cognitive development paired with marked reductions in frontal gray and white matter, further supporting the association between prenatal immune challenge and alterations in offspring neurodevelopment.

Methylation levels at specific CpG positions in the genome have been used to develop accurate estimators of chronological age in humans, mice, and other species. Although epigenetic clocks are generally species-specific, the principles underpinning them appear to be conserved at least across the mammalian class. This is exemplified by the successful development of epigenetic clocks for mice and several other mammalian species. Here, we describe epigenetic clocks for the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate in biological research. Using a custom methylation array (HorvathMammalMethylChip40), we profiled n = 281 tissue samples (blood, skin, adipose, kidney, liver, lung, muscle, and cerebral cortex). From these data, we generated five epigenetic clocks for macaques. These clocks differ with regard to applicability to different tissue types (pan-tissue, blood, skin), species (macaque only or both humans and macaques), and measure of age (chronological age versus relative age). Additionally, the age-based human-macaque clock exhibits a high age correlation (R = 0.89) with the vervet monkey (Chlorocebus sabaeus), another Old World species. Four CpGs within the KLF14 promoter were consistently altered with age in four tissues (adipose, blood, cerebral cortex, skin). Future studies will be needed to evaluate whether these epigenetic clocks predict age-related conditions in the rhesus macaque.

Abstract Background Considering the relationship between human morphology and physiology with the Rhesus monkey, this animal is the most prominent species of laboratory primate for human and animal health research. Moreover, sending Macaca mulatta monkey into space and simulating a living environment for humans shows the similarity of this animal's physiology with humans. Objective So far, no comprehensive study has been done on computed tomography (CT) scan and radiography of skulls in Rhesus monkeys. Therefore, providing accurate documents from the CT anatomy of the skull in these animals can help us to better understand normal conditions and diseases, and we can use a functional atlas of diagnostic imaging from the skull of this animal. Methods Ten mature monkeys weighing 6.5 kg were used for this project (five males and five females). A radiographic examination with standard views was performed during general anaesthesia. Then the monkeys were placed in a spherical CT scan during general anaesthesia with standard sternal recumbency. Results The frontal bone was seen as two parallel radiopaque lines coming forward and downward. The frontal sinus in the Rhesus monkey was not visible in both lateral and dorsoventral radiographs, which could indicate the degeneration of this sinus in this species. The number of teeth in an adult monkey was 32. Molar teeth had a bilophodont arrangement. Conclusions The comparison between the size of the eye ball in human and Rhesus monkey, unlike other measured parameters, did not differ much, and this indicates that the volume ratio of the eye ball to the whole skull in Rhesus monkey is higher than that of humans.

Objective: Rhesus monkeys are increasingly used in biomedical research, which makes their hematological and biochemical parameters increasingly important in preclinical research. Since age and sex can influence blood parameters, establishing reference intervals for such parameters based on age and sex becomes along with identifying the effect of age and sex on those parameters. Methods: A total of 1385 healthy Chinese rhesus monkeys (548 males and 837 females) anesthetized with ketamine were selected and segregated by age (six groups) and sex. A total of 21 hematological and 26 biochemical parameters were measured, and the effects of age and sex were analyzed. Results: We established baseline indices for hematological and biochemical parameters based on age and sex, separately, and observed significant impacts of age, sex, and age‐sex interactions on blood parameters. Among different age groups, significant differences were found in WBC, NEUT%, LYM%, EO%, LYM#, EO#, MCV, RDW‐CV, PLT, MPV, PDW, PCT, TP, Alb, GLB, A/G, ALT, AST, ALP, TBIL, GGT, BUN, Cre, GLU, CK, TRIG, LDL, HCY, IL‐6 FOL, Vit B12, VIT D‐T, PTH, and AMH. Additionally, significant differences were observed in RBC, HGB, HCT, MPV, Alb, BUN, Cre, GLU, CHOL, TRIG, HDL, LDL, HCY, and VIT D‐T between the two sexes. An age‐sex interaction exerted a significant effect on WBC, NEUT#, MCV, MCHC, PDW, GLB, ALP, Cre, CHOL, TRIG, HDL, LDL, HCY, IL‐6, Vit B12, VIT D‐T. However, neither age, sex, and age‐sex interactions exerted significant effects on MO%, MOMO#, MCH, RDW‐SD, CRP, and CT. Conclusion: Our study investigated the blood parameters of rhesus monkeys to provide a reference basis for rhesus monkey‐related scientific experimental research. [ABSTRACT FROM AUTHOR]

The brain of a rhesus monkey that died at 43 years of age with symptoms of suspected cognitive dysfunction was analyzed. pathological analyses revealed characteristic Alzheimer’s disease-related lesions: the aggregation of amyloid β (Aβ) in the form of senile plaques and phosphorylated tau proteins. We also revealed that Aβ43, which is prone to aggregation and toxicity in humans, is involved in senile plaques in the brain of the rhesus monkey, as well as several other Aβ species. Comparative studies of neuropathology using aged nonhuman primates lack behavioral descriptions compared to human medicine. This case report showed behavioral abnormalities and the detailed pathological changes that may have caused it in a super-aged rhesus monkey [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) are mobile DNA entities that can move within the host genome. Over long periods of evolutionary time, TEs are typically silenced via the accumulation of mutations in the genome, ultimately resulting in their immobilization. However, they still play an important role in the host genome by acting as regulatory elements. They influence host transcription in various ways, one of which as the origin of the generation of microRNAs (miRNAs), which are so-called miRNAs derived from TEs (MDTEs). miRNAs are small non-coding RNAs that are involved in many biological processes by regulating gene expression at the post-transcriptional level. Here, we identified MDTEs in the Macaca mulatta (rhesus monkey) genome, which is phylogenetically close species to humans, based on the genome coordinates of miRNAs and TEs. The expression of 5 out of 17 MDTEs that were exclusively registered in M. mulatta from the miRBase database (v22) was examined via quantitative polymerase chain reaction (qPCR). Moreover, Gene Ontology analysis was performed to examine the functional implications of the putative target genes of the five MDTEs. [ABSTRACT FROM AUTHOR]

Background: The sensory and mobility failure associated with spinal cord injury (SCI) is desperately complicated due to the pathological events that occur sequentially in consequent to the injury. Objectives: Herein, we applied neural stem cells, derived from human iPSCs (hiPSC-NSCs), to ameliorate the behavioral complications of contusive SCI in Rhesus monkeys, in sub-acute phase. Methods: hiPSC-NSCs were maintained and characterized in vitro for general NSCs as well as hind-limb specific gene and protein expression prior to transplantation. Moreover, Masson's trichrome staining (MTS) in addition to luxol fast blue (LFB) were performed to determine the fibrotic scar reduction and myelination respectively. Tarlov's scale were utilized to score the motor improvement, plus, sensory perception evaluation throughout six months following the injury. Results: hiPSC-NSCs were identified to own NSCs' exclusive properties in vitro by SOX2, DCX and NESTIN in addition to NESTIN, PAX6, SOX1, HOXA2 and HOXB2 protein and gene expression. Additionally, hiPSC-NSCs caused remarkable depletion in fibrotic scar and enhance myelination; spinal shock, sensory responses, reflexes and motor function were improved over six months. Conclusions: Our findings suggest that hiPSC-NSCs lead to promising recovery after SCI, therefore, this source of NSCs provide a therapeutic potential in clinical studies. [ABSTRACT FROM AUTHOR]

Aged rhesus monkeys, like aged humans, show declines in cognitive function. We present cognitive test data from a large sample of male and female rhesus monkeys, 34 young (aged 3.5–13.6 years) and 71 aged (aged 19.9–32.5 years at the start of cognitive testing). Monkeys were tested on spatiotemporal working memory (delayed response), visual recognition memory (delayed nonmatching to sample), and stimulus-reward association learning (object discrimination), tasks with an extensive evidence base in nonhuman primate neuropsychology. On average, aged monkeys performed worse than young on all 3 tasks. Acquisition of delayed response and delayed nonmatching to sample was more variable in aged monkeys than in young. Performance scores on delayed nonmatching to sample and object discrimination were associated with each other, but neither was associated with performance on delayed response. Sex and chronological age were not reliable predictors of individual differences in cognitive outcome among the aged monkeys. These data establish population norms for multiple cognitive tests in young and aged rhesus monkeys in the largest sample reported to date. They also illustrate independence of cognitive aging in task domains dependent on the prefrontal cortex and medial temporal lobe. [ABSTRACT FROM AUTHOR]

IntroductionAlzheimer's disease (AD) is a devastating condition with no effective treatments, with promising findings in rodents failing to translate into successful therapies for patients.MethodsTargeting the vulnerable entorhinal cortex (ERC), rhesus monkeys received two injections of an adeno-associated virus expressing a double tau mutation (AAV-P301L/S320F) in the left hemisphere, and control AAV-green fluorescent protein in the right ERC. Noninjected aged-matched monkeys served as additional controls.ResultsWithin 3 months we observed evidence of misfolded tau propagation, similar to what is hypothesized to occur in humans. Viral delivery of human 4R-tau also coaptates monkey 3R-tau via permissive templating. Tau spreading is accompanied by robust neuroinflammatory response driven by TREM2+ microglia, with biomarkers of inflammation and neuronal loss in the cerebrospinal fluid and plasma.DiscussionThese results highlight the initial stages of tau seeding and propagation in a primate model, a more powerful translational approach for the development of new therapies for AD.

The expression of linear DNA sequence is precisely regulated by the three-dimensional (3D) architecture of chromatin. Morphine-induced aberrant gene networks of neurons have been extensively investigated; however, how morphine impacts the 3D genomic architecture of neurons is still unknown. Here, we applied digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons. After receiving continuous morphine administration for 90 days on rhesus monkeys, we discovered that morphine re-arranged chromosome territories, with a total of 391 segmented compartments being switched. Morphine altered over half of the detected topologically associated domains (TADs), most of which exhibited a variety of shifts, followed by separating and fusing types. Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops. Moreover, all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops, and were further validated for changed expression. Collectively, an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects. Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

ASP8062 is an orally available GABAB receptor positive allosteric modulator (PAM). This study assessed the potential of ASP8062 for treating opioid use disorder (OUD). Three rhesus monkeys were pretreated with ASP8062 (0.3, 1 or 3 mg/kg) by oral administration 1 h prior to a 2-h morphine self-administration session (0.03 mg/kg, iv, per injection) under a fixed-ratio 5 schedule. We further examined the potential worsening of morphine-induced respiratory suppression by ASP8062 after coadministration of morphine (10 mg/kg, sc) and ASP8062 (10 mg/kg, po) in cynomolgus monkeys using a custom-made whole-body plethysmograph. Plasma concentrations of ASP8062 (3 or 10 mg/kg, po) were assessed in cynomolgus monkeys using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). ASP8062 at 3 mg/kg, po decreased the morphine self-administrations with significant differences from the vehicle-treated group (IC50 = 0.97 ± 0.36 mg/kg). Exposure levels at 3 mg/kg observed in monkeys were comparable to the clinical exposure levels which positive pharmacodynamic effects were previously shown. Further, ASP8062 did not potentiate morphine-induced respiratory suppression up to exposure levels higher than the clinically relevant dose. ASP8062 may reduce opioid use in OUD patients without affecting respiratory system, providing justification for further ASP8062 development as a potential treatment option for OUD.

The prenatal period is a developmental stage of peak sensitivity, during which environmental exposures can program post-natal developmental outcomes. Prenatal stress, in particular, has often been associated with detrimental neurobehavioral outcomes like mood and anxiety disorders. In the present study, we examined the effects of a stressful prenatal maternal experience (maternal relocation during pregnancy) on the post-partum development of offspring in rhesus macaques. To help isolate the effects of prenatal stress from genetic predispositions and post-natal experience, we compared biologically reared infants (infants raised with their biological mothers) with cross-fostered infants (those raised by non-related females in new social groups). We examined the effects of prenatal relocation stress on measures collected at 3-4 months of age during a standardized biobehavioral assessment. Unexpectedly, we found that prenatal stress resulted in a behavioral pattern consistent with resilience rather than anxiety: prenatal stress was linked with greater activity, lower anxiety, and more interaction with novel objects, as well as higher ratings of temperamental confidence during assessment. These effects were observed in infants reared by biological mothers as well as cross-fostered infants, suggesting that the effects of prenatal stress were not attributable to maternal genetics or post-natal factors. Our surprising results suggest that prenatal relocation stress may confer resilience in infant rhesus monkeys.

Rod and cone photoreceptors differ in their shape, photopigment expression, synaptic connection patterns, light sensitivity, and distribution across the retina. Although rods greatly outnumber cones, human vision is mostly dependent on cone photoreceptors since cones are essential for our sharp visual acuity and color discrimination. In humans and other primates, the fovea centralis (fovea), a specialized region of the central retina, contains the highest density of cones. Despite the vast importance of the fovea for human vision, the molecular mechanisms guiding the development of this region are largely unknown. MicroRNAs (miRNAs) are small post-transcriptional regulators known to orchestrate developmental transitions and cell fate specification in the retina. Here, we have characterized the transcriptional landscape of the developing rhesus monkey retina. Our data indicates that non-human primate fovea development is significantly accelerated compared to the equivalent retinal region at the other side of the optic nerve head, as described previously. Notably, we also identify several miRNAs differentially expressed in the presumptive fovea, including miR-15b-5p, miR-342-5p, miR-30b-5p, miR-103-3p, miR-93-5p as well as the miRNA cluster miR-183/-96/-182. Interestingly, miR-342-5p is enriched in the nasal primate retina and in the peripheral developing mouse retina, while miR-15b is enriched in the temporal primate retina and increases over time in the mouse retina in a central-to-periphery gradient. Together our data constitutes the first characterization of the developing rhesus monkey retinal miRNome and provides novel datasets to attain a more comprehensive understanding of foveal development.

A bacterium was isolated and identified from the secretion of a rhesus monkey with endometritis. The morphological results showed that the strain exhibited round, convex, gray-white colonies with smooth surfaces and diameters ranging from 1 to 2 mm when cultured on Columbia blood agar at 37 °C for 24 h; on salmonella–shigella agar (S.S.) at 37 °C for 24 h, the colonies appeared round, flat, and translucent. Gram staining showed negative results with blunt ends and non-spore-forming characteristics. Molecular biology results showed that the 16S rRNA sequence of the strain revealed over 96.9% similarity with published sequences of M. morganii from different sources in the NCBI GenBank database. Morphological and molecular biology analysis confirmed that the strain (RM2023) isolated from cervical secretions of rhesus monkey was M. morganii. Drug sensitivity testing demonstrated that the isolated strain (RM2023) was sensitive to ceftriaxone, amikacin, gentamicin, cefazolin, cefuroxime, ceftazidime, levofloxacin, cotrimoxazole, norfloxacin, and tetracycline; moderately sensitive to ampicillin; and resistant to penicillin, vancomycin, ciprofloxacin, and clindamycin. The research findings provide valuable insights for disease prevention in rhesus monkeys and contribute to molecular epidemiological studies.

Background: Considering the relationship between human morphology and physiology with the Rhesus monkey, this animal is the most prominent species of laboratory primate for human and animal health research. Moreover, sending Macaca mulatta monkey into space and simulating a living environment for humans shows the similarity of this animal's physiology with humans. Objective: So far, no comprehensive study has been done on computed tomography (CT) scan and radiography of skulls in Rhesus monkeys. Therefore, providing accurate documents from the CT anatomy of the skull in these animals can help us to better understand normal conditions and diseases, and we can use a functional atlas of diagnostic imaging from the skull of this animal. Methods: Ten mature monkeys weighing 6.5 kg were used for this project (five males and five females). A radiographic examination with standard views was performed during general anaesthesia. Then the monkeys were placed in a spherical CT scan during general anaesthesia with standard sternal recumbency. Results: The frontal bone was seen as two parallel radiopaque lines coming forward and downward. The frontal sinus in the Rhesus monkey was not visible in both lateral and dorsoventral radiographs, which could indicate the degeneration of this sinus in this species. The number of teeth in an adult monkey was 32. Molar teeth had a bilophodont arrangement. Conclusions: The comparison between the size of the eye ball in human and Rhesus monkey, unlike other measured parameters, did not differ much, and this indicates that the volume ratio of the eye ball to the whole skull in Rhesus monkey is higher than that of humans. [ABSTRACT FROM AUTHOR]

Background: The prevalence and severity of periodontitis demonstrates altered population distribution with age, sex, and race and ethnicity. While males exhibit greater frequency of disease, particularly with aging, the underlying basis for this observation remains obscure. Objective: This study used a nonhuman primate (Macaca mulatta) model of experimental ligature‐induced periodontitis in adult animals to evaluate gingival transcriptomic differences stratified based upon sex of the animal. Methods: The 18 animals represented humans ages 40–80 years, with gingival tissue samples obtained at baseline, 0.5 months (initiation), 1 and 3 months (progression), and at 5 months that were 60 days after ligature removal for clinical disease resolution. Microarray analysis was used to quantify gene expression profiles in the gingival tissues. Results: The results demonstrated clear gene expression differences in healthy (baseline) tissues between the sexes, with elevations in females associated with immune responses and elevation in males related to tissue structural genes. With disease initiation, fewer genes differed between the sexes, while these differences were significantly increased in progressing disease and resolution, particularly in male animals. Overexpressed biological processes showed tissue structural/functional genes at initiation, with host response pathways altered during disease progression. Resolution samples generally demonstrated biological processes of cellular metabolism that differed from baseline healthy samples. Conclusion: The transcriptomic findings support sex as a biological variable in periodontitis using a nonhuman primate model of experimental periodontitis. [ABSTRACT FROM AUTHOR]

Purpose: Exposure to blue light is thought to be harmful to the retina. The purpose of this study was to determine the effects of long-term exposure to narrowband blue light on retinal function in rhesus monkeys. Methods: Young rhesus monkeys were reared under short-wavelength "blue" light (n = 7; 465 nm, 183 ± 28 lx) on a 12-h light/dark cycle starting at 26 ± 2 days of age. Age-matched control monkeys were reared under broadband "white" light (n = 8; 504 ± 168 lx). Light- and dark-adapted full-field flash electroretinograms (ERGs) were recorded at 330 ± 9 days of age. Photopic stimuli were brief red flashes (0.044–5.68 cd.s/m2) on a rod-saturating blue background and the International Society for Clinical Electrophysiology of Vision (ISCEV) standard 3.0 white flash on a 30 cd/m2 white background. Monkeys were dark adapted for 20 min and scotopic stimuli were ISCEV standard white flashes of 0.01, 3.0, and 10 cd.s/m2. A-wave, b-wave, and photopic negative response (PhNR) amplitudes were measured. Light-adapted ERGs in young monkeys were compared to ERGs in adult monkeys reared in white light (n = 10; 4.91 ± 0.88 years of age). Results: For red flashes on a blue background, there were no significant differences in a-wave (P = 0.46), b-wave (P = 0.75), and PhNR amplitudes (P = 0.94) between white light and blue light reared monkeys for all stimulus energies. ISCEV standard light- and dark-adapted a- and b-wave amplitudes were not significantly different between groups (P > 0.05 for all). There were no significant differences in a- and b-wave implicit times between groups for all ISCEV standard stimuli (P > 0.05 for all). PhNR amplitudes of young monkeys were significantly smaller compared to adult monkeys for all stimulus energies (P < 0.05 for all). There were no significant differences in a-wave (P = 0.19) and b-wave (P = 0.17) amplitudes between young and adult white light reared monkeys. Conclusions: Long-term exposure to narrowband blue light did not affect photopic or scotopic ERG responses in young monkeys. Findings suggest that exposure to 12 h of daily blue light for approximately 10 months does not result in altered retinal function. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the increase of age, the structure and function of the spleen changed, and the thymus gradually atrophied and degenerated after puberty, resulting in immune dysfunction. OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells on the structure and function of thymus and spleen in aging rhesus monkeys. METHODS: Six aging rhesus monkeys with an average age of 25 years were randomly divided into elderly group (n=3) and elderly treatment group (n=3). Rhesus monkeys in the elderly treatment group were infused with the 4th generation bone marrow mesenchymal stem cells (1×107 /kg) labeled with superparamagnetic iron nanoparticles through femoral vein once a day for 3 consecutive days. Rhesus monkeys in the elderly group were infused with the same volume of normal saline at the same time. The rhesus monkeys were euthanized 5 months after the last infusion of bone marrow mesenchymal stem cells. The thymus and spleen tissues were obtained. The structural changes of thymus and spleen tissues were observed by hematoxylin and eosin staining. Immunofluorescence staining was used to analyze the expression of T cell subsets and age-related gene protein P21 in thymus tissues. Immunohistochemical staining was used to analyze the expression of T cell subsets and age-related gene protein P21 in spleen tissues. Before euthanized, 5 mL of femoral venous blood was extracted by heparin tube. The levels of tumor necrosis factor-α and interleukin-1α in peripheral blood serum were analyzed by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: (1) Superparamagnetic iron nanoparticles labeled bone marrow mesenchymal stem cells could colonize and play a role in aging thymus and spleen tissues in rhesus monkeys. (2) After transplantation of bone marrow mesenchymal stem cells, the cortex and medulla junction appeared in some tissues of the aged rhesus monkeys, and the adipocytes decreased, and the thymic body appeared, and the structure of thymus changed to normal. The splenic tissue of aged rhesus monkeys showed a clear boundary between red pulp and white pulp, and the edge of the splenic body was more complete, and the macrophages were reduced, and the structure of spleen tissue changed to normal. (3) Compared with the elderly group, the expression of CD3+, CD4+ and CD8+ T cells in senile thymus and spleen tissues in the elderly treatment group showed a trend of increase. The expression of P21 protein in senile thymus and spleen tissues in the elderly treatment group showed a significant downward trend. (4) Compared with the elderly group, the levels of tumor necrosis factor-α and interleukin-1α in peripheral blood of the elderly treatment group showed a significant downward trend. (5) These results indicated that transplantation of bone marrow mesenchymal stem cells could improve the structure and function of thymus and spleen tissues in aged rhesus monkeys. [ABSTRACT FROM AUTHOR]

The presence of bronchus-associated lymphoid tissue (BALT) and its size in humans largely depends upon age. It is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. Environmental gases or allergens may have an effect on the number of BALT. Lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of BALT after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of house dust mite or a combination of ozone and house dust mite for 12 months. In the lungs of monkeys housed in filtered air for 2 months, no BALT was identified. After 6, 12, or 36 months, the number of BALT showed a significantly increased correlation with age in monkeys housed in filtered air. After 2 months of episodic house dust mite (HDM) exposure, no BALT was found. Monkeys exposed to HDM or HDM + ozone did not show a significant increase in BALT compared to monkeys housed in filtered air. However, monkeys exposed to ozone alone did show significant increases in BALT compared to all other groups. In particular, there were frequent accumulations of lymphocytes in the periarterial space of ozone exposed animals. In conclusion, BALT in rhesus monkeys housed under filtered air conditions is age-dependent. BALT significantly increased in monkeys exposed to ozone in comparison with monkeys exposed to HDM.

The use of 89Zr-antibody PET imaging to measure antibody biodistribution and tissue pharmacokinetics is well established, but current PET systems lack the sensitivity needed to study 89Zr-labeled antibodies beyond 2-3 isotope half-lives (7-10 d), after which a poor signal-to-noise ratio is problematic. However, studies across many weeks are desirable to better match antibody circulation half-life in human and nonhuman primates. These studies investigated the technical feasibility of using the primate mini-EXPLORER PET scanner, making use of its high sensitivity and 45-cm axial field of view, for total-body imaging of 89Zr-labeled antibodies in rhesus monkeys up to 30 d after injection. Methods: A humanized monoclonal IgG antibody against the herpes simplex viral protein glycoprotein D (gD) was radiolabeled with 89Zr via 1 of 4 chelator-linker combinations (benzyl isothiocyanate-DFO [DFO-Bz-NCS], where DFO is desferrioxamine B; DFO-squaramide; DFO*-Bz-NCS, where DFO* is desferrioxamine*; and DFO*-squaramide). The pharmacokinetics associated with these 4 chelator-linker combinations were compared in 12 healthy young male rhesus monkeys (∼1-2 y old, ∼3 ± 1 kg). Each animal was initially injected intravenously with unlabeled antibody in a peripheral vessel in the right arm (10 mg/kg, providing therapeutic-level antibody concentrations), immediately followed by approximately 40 MBq of one of the 89Zr-labeled antibodies injected intravenously in a peripheral vessel in the left arm. All animals were imaged 6 times over a period of 30 d, with an initial 60-min dynamic scan on day 0 (day of injection) followed by static scans of 30-45 min on approximately days 3, 7, 14, 21, and 30, with all acquired using a single bed position and images reconstructed using time-of-flight list-mode ordered-subsets expectation maximization. Activity concentrations in various organs were extracted from the PET images using manually defined regions of interest. Results: Excellent image quality was obtained, capturing the initial distribution phase in the whole-body scan; later time points showed residual 89Zr mainly in the liver. Even at 30 d after injection, representing approximately 9 half-lives of 89Zr and with a total residual activity of only 20-40 kBq in the animal, the image quality was sufficient to readily identify activity in the liver, kidneys, and upper and lower limb joints. Significant differences were noted in late time point liver uptake, bone uptake, and whole-body clearance between chelator-linker types, whereas little variation (±10%) was observed within each type. Conclusion: These studies demonstrate the ability to image 89Zr-radiolabeled antibodies up to 30 d after injection while maintaining satisfactory image quality, as provided by the primate mini-EXPLORER with high sensitivity and long axial field of view. Quantification demonstrated potentially important differences in the behavior of the 4 chelators. This finding supports further investigation.