Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys.

BACKGROUND: Benzodiazepines bind to γ-aminobutyric acid type A (GABAA) receptor subtypes identified by different α subunits (i.e., α1GABAA, α2GABAA, α3GABAA, and α5GABAA). Sedative-motor effects of benzodiazepines are thought to involve α1GABAA and α3GABAA subtypes. AIMS: We evaluated observable measures of sedative-motor effects and species-typical behaviors in monkeys following acute administration of novel GABAkines (positive allosteric modulators of GABAA receptors), with varying degrees of selective efficacy at different GABAA receptor subtypes. We predicted that the induction of sedative-motor effects would depend on the degree of α1GABAA and α3GABAA efficacy. METHODS: Adult female rhesus monkeys (N = 4) were implanted with chronic indwelling i.v. catheters. Quantitative behavioral observation was conducted by trained observers following administration of multiple doses of the conventional benzodiazepine alprazolam and the GABAkines MP-III-80 (preferential efficacy at α2/α3/α5GABAA subtypes), KRM-II-81, MP-III-24 (both with preferential efficacy for α2/α3GABAA subtypes), and MP-III-22 (preferential potency and efficacy for α5GABAA subtypes). RESULTS: As with alprazolam, all GABAkines induced significant levels of mild sedation ("rest/sleep posture"). Deep sedation was observed with alprazolam, MP-III-80, and MP-III-22; motoric effects (observable ataxia) were obtained with alprazolam, KRM-II-81, and MP-III-22 only. Surprisingly, the order of potency for rest/sleep posture was significantly associated only with potency at α5GABAA subtypes. CONCLUSIONS: GABAkines with preferential efficacy at α2/α3GABAA and/or α5GABAA subtypes engendered sedative-motor effects in monkeys, although only compounds with α5GABAA activity engendered deep sedation. Moreover, the significant relationship between potency obtained with in vitro electrophysiology data and the rest/sleep posture measure suggests a role for the α5GABAA subtype in this milder form of sedation.

White matter lipid alterations during aging in the rhesus monkey brain.

The brain of higher organisms, such as nonhuman primates, is particularly rich in lipids, with a gray to white matter ratio of approximately 40 to 60%. White matter primarily consists of lipids, and during normal aging, it undergoes significant degeneration due to myelin pathology, which includes structural abnormalities, like sheath splitting, and local inflammation. Cognitive decline in normal aging, without neurodegenerative diseases, is strongly linked to myelin pathology. Although the exact cause of myelin damage is unclear, older myelin differs from younger myelin, as shown by electron microscopy and altered expression of myelin-related RNAs. However, changes in lipid composition during brain aging remain poorly understood. This study assessed lipid profiles from the frontal lobe corpus callosum, an area where age-related myelin pathology is linked to cognitive decline. Results showed significant changes in lipids with age, revealing distinct age-related profiles. Some lipids that are enriched in myelin sheaths become more saturated, while important structural components, like ceramides, decrease. Disease-associated biomarkers such as cholesterol ester Che (22:6) and sulfatide ST (42:2) also change in older monkeys. Additionally, gene expression of lipid biosynthetic enzymes declines with age, while lipid peroxidation remains stable in the same brain region. This suggests that changes in lipid biosynthesis, rather than oxidative damage, likely account for the differences in lipid composition. Our findings indicate that myelin in the normal aging monkey brain shows diverse lipid changes, which may relate to age-related myelin pathology and could constitute targets for designing nutrient supplements or drugs to rejuvenate the brain's lipidome.

A rhesus macaque intragastric challenge model for evaluating the safety, immunogenicity, and efficacy of live-attenuated Shigella dysenteriae 1 vaccine candidates.

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 rhesus macaque challenge model to evaluate the safety, immunogenicity, and efficacy of five live-attenuated Shigella dysenteriae 1 vaccine candidates, all derived from the 1617 parent strain. The vaccine strains included WRSd1, 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.

Therapeutic efficacy and in vivo distribution of human umbilical cord-derived mesenchymal stem cell spheroids transplanted via B-Ultrasound-guided percutaneous portal vein puncture in rhesus monkey models of liver fibrosis.

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-ß1/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.

Allometric comparison of viral dynamics in the nasal cavity-nasopharyngeal mucus layer of human and rhesus monkey by CFD-HCD approach.

BACKGROUND AND OBJECTIVE: Viral respiratory infections stand as a considerable global health concern, presenting significant risks to the health of both humans and animals. This study aims to conduct a preliminary analysis of the time series of viral load in the nasal cavity-nasopharynx (NC-NP) of the human and rhesus macaque (RM). METHODS: Taking into account the random uniform distribution of virus-laden droplets with a diameter of 10 µm in the mucus layer, this study applies the computational fluid dynamics-host cell dynamics (CFD-HCD) method to 3D-shell NC-NP models of human and RM, analyzing the impact of initial distribution of droplets on the viral dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), estimating parameters in the HCD model based on experimental data, integrating them into simulations to predict the time series of viral load and cell counts, and being visualized. The reproductive number (R0) are calculated to determine the occurrence of infection. The study also considers cross-parameter combinations and cross-experimental datasets to explore potential correlations between the human and RM. RESULTS: The research findings indicate that the uniform distribution of virus-laden droplets throughout the whole NC-NP models of human and RM is reasonable for simulating and predicting viral dynamics. The visualization results offer dynamic insights into virus infection over a period of 20 days. Studies involving parameter and dataset exchanges between the two species underscore certain similarities in predicting virus infections between the human and RM. CONCLUSIONS: This study lays the groundwork for further exploration into the parallels and distinctions in respiratory virus dynamics between humans and RMs, thus aiding in making more informed decisions in research and experimentation.

Complete genome sequences of Clostridium perfringens CP201 isolated from an asymptomatic rhesus monkey (Macaca mulatta).

Clostridium perfringens is a leading cause of human gastroenteritis. The genome sequence of C. perfringens CP201 from an asymptomatic rhesus monkey, Macaca mulatta, consists of one chromosome (3,241,413 bp; 30.22% G + C) and one plasmid (92,983 bp; 28.43% G + C), encoding 2,935 genes, 94 tRNAs, 30 rRNAs, and 1 CRISPR array.

The Efficiency of In Vitro Differentiation of Primate iPSCs into Cardiomyocytes Depending on Their Cell Seeding Density and Cell Line Specificity.

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.

Myelin dystrophy impairs signal transmission and working memory in a multiscale model of the aging prefrontal cortex.

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.

Proteomic features of gray matter layers and superficial white matter of the rhesus monkey neocortex: comparison of prefrontal area 46 and occipital area 17.

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.

AAV5 Delivery of CRISPR/Cas9 Mediates Genome Editing in the Lungs of Young Rhesus Monkeys.

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.

Evaluation of [18F]fluoroestradiol and ChRERα as a gene expression PET reporter system in rhesus monkey brain.

Positron emission tomography (PET) reporter systems are a valuable means of estimating the level of expression of a transgene in vivo. For example, the safety and efficacy of gene therapy approaches for the treatment of neurological and neuropsychiatric disorders could be enhanced via the monitoring of exogenous gene expression levels in the brain. The present study evaluated the ability of a newly developed PET reporter system [18F]fluoroestradiol ([18F]FES) and the estrogen receptor-based PET reporter ChRERα, to monitor expression levels of a small hairpin RNA (shRNA) designed to suppress choline acetyltransferase (ChAT) expression in rhesus monkey brain. The ChRERα gene and shRNA were expressed from the same transcript via lentivirus injected into monkey striatum. In two monkeys that received injections of viral vector, [18F]FES binding increased by 70% and 86% at the target sites compared with pre-injection, demonstrating that ChRERα expression could be visualized in vivo with PET imaging. Post-mortem immunohistochemistry confirmed that ChAT expression was significantly suppressed in regions in which [18F]FES uptake was increased. The consistency between PET imaging and immunohistochemical results suggests that [18F]FES and ChRERα can serve as a PET reporter system in rhesus monkey brain for in vivo evaluation of the expression of potential therapeutic agents, such as shRNAs.

Complete genome sequences of Campylobacter jejuni subsp. jejuni strain P4549 isolated from an asymptomatic rhesus monkey (Macaca mulatta).

Campylobacter jejuni subsp. jejuni is a leading bacterial cause of human gastroenteritis. C. jejuni strain P4549 was isolated from an asymptomatic rhesus monkey, Macaca mulatta. We report the genome sequences have a circular chromosome of 1,729,940 bp and two plasmids of 50,482 bp and 7,259 bp, respectively.

Isolation and Identification of Morganella morganii from Rhesus Monkey (Macaca mulatta) in China.

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.

Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age.

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.

SIRT1 activation ameliorates rhesus monkey liver fibrosis by inhibiting the TGF-ß/smad signaling pathway.

TGF-ß/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet (HFD) for two years. And the liver function was further determined by serum biochemical tests. The mRNA levels and protein expression of rat hepatic stellate (HSC-T6) cells were determined after treatment with Resveratrol (RSV) and Nicotinamide (NAM), respectively. The results showed that with the increasing of hepatic fibrosis in rhesus monkeys, the liver function impaired, and the transforming growth factor-ß1 (TGF-ß1), p-Smad3 (p-Smad3) and alpha-smooth muscle actin (α-SMA) was up-regulated, while SIRT1 and Smad7 were down-regulated. Moreover, when stimulated the HSC-T6 with RSV to activate SIRT1 for 6, 12, and 24 h, the results showed that RSV promoted the expression of smad7, while the expression of TGF-ß1, p-Smad3 and α-SMA were inhibited. In contrast, when the cells stimulated with NAM to inhibit SIRT1 for 6, 12, and 24 h, the Smad7 expression was decreased, while TGF-ß1, p-Smad3, and α-SMA expressions were increased. These results indicate that SIRT1 acts as an important protective factor for liver fibrosis, which may be attributed to inhibiting the signaling pathway of TGF-ß/Smad in hepatic fibrosis of the rhesus monkey.

Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey.

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.

Safety and Pharmacokinetic Assessment of the FIC CLDN18.2/4-1BB Bispecific Antibody in Rhesus Monkeys.

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.

Identification of microRNAs Derived from Transposable Elements in the Macaca mulatta (Rhesus Monkey) Genome.

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.

An expedition in the jungle of pluripotent stem cells of non-human primates.

For nearly three decades, more than 80 embryonic stem cell lines and more than 100 induced pluripotent stem cell lines have been derived from New World monkeys, Old World monkeys, and great apes. In this comprehensive review, we examine these cell lines originating from marmoset, cynomolgus macaque, rhesus macaque, pig-tailed macaque, Japanese macaque, African green monkey, baboon, chimpanzee, bonobo, gorilla, and orangutan. We outline the methodologies implemented for their establishment, the culture protocols for their long-term maintenance, and their basic molecular characterization. Further, we spotlight any cell lines that express fluorescent reporters. Additionally, we compare these cell lines with human pluripotent stem cell lines, and we discuss cell lines reprogrammed into a pluripotent naive state, detailing the processes used to attain this. Last, we present the findings from the application of these cell lines in two emerging fields: intra- and interspecies embryonic chimeras and blastoids.

Senile plaques and phosphorylated tau deposition in a super-aged rhesus monkey (Macaca mulatta).

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 ß (Aß) in the form of senile plaques and phosphorylated tau proteins. We also revealed that Aß43, 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 Aß 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.