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Macaca mulatta

Macaca mulatta, also known as the rhesus macaque, is a widely used nonhuman primate model in biomedical research.
This Old World monkey species is native to parts of Asia and is known for its adaptability, social intelligence, and genetic similarity to humans.
Macaca mulatta has been extensively studied in fields such as neuroscience, immunology, and developmental biology, contributing to our understanding of human health and disease.
Researchers can optimize their Macaca mulatta studies with PubCompare.ai, an AI-powered tool that helps locate the best protocols from literature, preprints, and patents.
With intelligent comparisons, PubCompare.ai can enhance reproducibility and accuracy in Macaca mulatta research, taking your studies to the next lavel.

Most cited protocols related to «Macaca mulatta»

Genotyping and Haplotyping of Human SNPs

Cited 756 times

Of approximately 6.9 million SNPs in dbSNP release 122 approximately 4.7 million were selected for genotyping by Perlegen. 2.5 million SNPs were excluded because no assay could be designed and a further 350,000 were excluded for other reasons (see Methods). Perlegen performed genotyping using custom high-density oligonucleotide arrays as previously described15 (link). Additional genotype submissions are described in the text. QC filters were applied as previously described3 (link). Where multiple submissions met the QC criteria the submission with the lowest missing data rate was chosen for inclusion in the non-redundant filtered data set. Haplotypes were estimated from genotype data as described previously3 (link). Ancestral states at SNPs were inferred by parsimony by comparison to orthologous bases in the chimpanzee (panTro2) and rhesus macaque (rheMac2) assemblies. Recombination rates and the location of recombination hotspots were estimated as described previously3 (link). Additional details can be found in the Methods section and the Supplementary Information. The data described in this paper are in release 21 of the International HapMap Project.

A second generation human haplotype map of over 3.1 million SNPs. (2007). Nature, 449(7164), 851-861.

Publication 2007

Biological Assay Genotype Haplotypes Macaca mulatta Oligonucleotide Arrays Pan troglodytes Recombination, Genetic Single Nucleotide Polymorphism

Differentiation and Characterization of Midbrain Dopaminergic Neurons

Cited 143 times

Human ESC (H9, H1) and iPSC lines (2C6 and SeV6) were subjected to a modified dual SMAD-inhibition^{13 (link)} based FP induction^{12 (link)} protocol. Exposure to SHH C25II, Purmorphamine, FGF8 and CHIR99021 were optimized for midbrain FP and DA neuron yield (see Figure 1d). Following FP induction, further maturation was carried out in Neurobasal/B27 medium supplemented with AA, BDNF, GDNF, TGFβ3 and dbcAMP (see full methods for details). The resulting DA neurons were subjected to extensive phenotypic characterization via immunocytochemistry, qRT-PCR, gene expression profiling, HPLC analysis for DA and in vitro electrophysiological recordings. In vivo studies were performed in 6-hydroxydopamine lesioned, hemiparkinsonian rodents (adult NOD-SCID IL2Rgc mice and Sprague Dawley rats) as well as in two adult rhesus monkeys treated with carotid injections of MPTP. DA neurons were injected stereotactically in the striata of the animals (150 × 10³ cells in mice, 250 × 10³ cells in rats) and a total of 7.5 × 10⁶ cells (distributed in 6 tracts; 3 on each side of brain) in monkeys. Behavioral assays were performed at monthly intervals post grafting, including amphetamine mediated rotational analysis as well as a test for focal akinesia (“stepping test”) and forelimb use (cylinder test). Rats and mice were sacrificed at 18–20 weeks and the primates at 1 month post grafting. Characterization of the grafts was performed via stereological analyses of cell numbers and graft volumes and comprehensive immunohistochemistry.

Kriks S., Shim J.W., Piao J., Ganat Y.M., Wakeman D.R., Xie Z., Carrillo-Reid L., Auyeung G., Antonacci C., Buch A., Yang L., Beal M.F., Surmeier D.J., Kordower J.H., Tabar V, & Studer L. (2011). Floor plate-derived dopamine neurons from hESCs efficiently engraft in animal models of PD. Nature, 480(7378), 547-551.

Publication 2011

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Adult Amphetamine Animals Biological Assay Brain Bucladesine Carotid Arteries Cells Chir 99021 FGF8 protein, human Forelimb Glial Cell Line-Derived Neurotrophic Factor Grafts High-Performance Liquid Chromatographies Homo sapiens Hydroxydopamine Immunocytochemistry Immunohistochemistry Induced Pluripotent Stem Cells Macaca mulatta Mesencephalon Mice, Inbred NOD Monkeys Mus Neurons Phenotype Primates purmorphamine Rats, Sprague-Dawley Rattus Rodent SCID Mice Step Test Striatum, Corpus

Comprehensive MHC Peptide Binding Dataset

Cited 130 times

Quantitative nonameric peptide–MHC class I binding data were obtained from the IEDB database (Sette et al. 2005a (link)) and an in-house database of quantitative peptide–MHC binding data. In total, the data set consisted of 79,137 unique peptide–MHC class I interactions covering 34 HLAA, 32 HLA-B, eight chimpanzee (Patr), seven rhesus macaque (Mamu), one gorilla (Gogo), and six mouse MHC class I alleles. See Supplementary Table S1 for a list of the number of data points per allele. The data are highly diverse containing a total number of 25,525 unique peptides. Only a minor fraction of the peptides (1,112 or 4%) share more than seven amino acid identity to any other peptide in the data set. The data set contains a large fraction of non-binding data for each allele (on average 70%). The low data redundancy and the large amount of non-binding data make this an ideal data set for machine learning data mining.
Qualitative nonameric MHC ligand data for HLA-A, HLA-B, HLA-C, and HLA-G were obtained from the SYFPEITHI database (Rammensee et al. 1999 (link)), and MHC ligand data for HLA-E*0101 were obtained from the IEDB (Sette et al. 2005a (link)).
Quantitative data for the swine MHC molecule SLA-1*0401 was obtained as described in the “Materials and methods”.
The evaluation data for HLA ligands and quantitative non-human primate peptide binding are available online at http://www.cbs.dtu.dk/suppl/immunology/NetMHCpan-2.0.php.

Hoof I., Peters B., Sidney J., Pedersen L.E., Sette A., Lund O., Buus S, & Nielsen M. (2008). NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics, 61(1), 1-13.

Publication 2008

Alleles Amino Acids Genes, MHC Class I Gorilla gorilla Histocompatibility Antigens Class I HLA-B Antigens HLA-C Antigens HLA-E antigen HLA-G Antigen Homo sapiens Ligands Macaca mulatta MHC binding peptide Mice, House Pan troglodytes peptide I Peptides Pigs Primates

Comprehensive Transcriptomic Profiling Across Species

Cited 69 times

We downloaded all the protein sequences of 65 animal genomes from Ensembl (version 75) (17 (link)) to identify their TFs, transcription co-factors and CRFs. We obtained most of the gene annotations from NCBI Entrez Gene and Ensembl databases, which includes basic information, orthologs, paralogs, phenotype, Gene Ontology (GO) and gene model. The protein–protein interaction information was parsed from BioGRID (18 (link)) and HPRD (19 (link)) databases. The pathway annotations were extracted from BioCarta (http://www.biocarta.com/) and KEGG databases. Putative functional domains were searched by PfamScan (ftp://ftp.ebi.ac.uk/pub/databases/Pfam/Tools/) program.
Rich information for gene expression is provided in AnimalTFDB 2.0. We downloaded the human gene expression data of cancers, tissues and cell lines from TCGA (https://tcga-data.nci.nih.gov/tcga/findArchives.htm) and EBI Expression Atlas (http://www.ebi.ac.uk/gxa/download.html). The expression data of the human proteome were parsed from two recent Nature papers (20 (link),21 (link)). The gene expression of Drosophila melanogaster and Caenorhabditis elegans was extracted from the data published by Li et al. (22 (link)). Our collaborators Drs Yu Xue and Haibo Jia kindly provided the unpublished gene expression data of Danio rerio. We downloaded the raw data for Rattus norvegicus, Bos taurus and Gallus gallus from NCBI GEO DataSets published by Burge group (16 (link)) and estimated gene expression levels with TopHat (23 (link)) and Cufflinks (24 (link)) programs. The gene expression data for Mus musculus and Macaca mulatta were downloaded from RhesusBase (25 (link),26 (link)), which were estimated from the RNA-Seq data published by groups Burge (16 (link)), Kaessmann (15 (link)) and Chuan-Yun Li (25 (link)).

Zhang H.M., Liu T., Liu C.J., Song S., Zhang X., Liu W., Jia H., Xue Y, & Guo A.Y. (2014). AnimalTFDB 2.0: a resource for expression, prediction and functional study of animal transcription factors. Nucleic Acids Research, 43(Database issue), D76-D81.

Publication 2014

Amino Acid Sequence Animals Bos taurus Caenorhabditis elegans Cell Lines Chickens Drosophila melanogaster Gene, Cancer Gene Annotation Gene Expression Genes Genome Homo sapiens Macaca mulatta Mice, House Phenotype Proteins Proteome Rattus norvegicus RNA-Seq Tissues Transcription Factor Zebrafish

Macaque SIV Challenge Model for Vaccine Evaluation

Cited 63 times

Sixty-eight purpose-bred male RM (Macaca mulatta) of Indian genetic descent were used in this study. RhCMV/SIV vectors were given subcutaneously at a dose of 5 × 10⁶ plaque-forming units per vector. DNA and Ad5 vectors were given intramuscularly at doses of 1.6 mg per vector and 2 × 10¹⁰ particle units per vector, respectively. RM were challenged intra-rectally with SIVmac239 using a repeated (weekly), limiting dose protocol^{5 (link)}. After the onset of infection (pvl ≥30 copy eq/ml), RM were followed weekly until onset of AIDS or a minimum of 224 days for progressive infection and 365 days for controlled infection. SIV- and RhCMV-specific CD4+ and CD8+ T cell responses were measured in mononuclear cell preparations from blood and tissues by flow cytometric intracellular cytokine analysis^{5 (link)}. SIVenv-specific Abs were determined by neutralization of tissue culture-adapted SIVmac251 using a luciferase reporter gene assay²². Levels of SIV RNA and DNA in plasma and from isolated cell preparations were quantified by standard quantitative real-time PCR and RT-PCR assays^{23 (link),24 (link)}. Tissue-associated SIV RNA and DNA at necropsy were quantified by an ultra-sensitive nested, quantitative real-time PCR and RT-PCR approach (see Full Methods). The presence of inducible, replication competent SIV in mononuclear cell preparations was detected by co-cultivation with CEMx174 cells, as previously described^{16 (link)}.

Hansen S.G., Ford J.C., Lewis M.S., Ventura A.B., Hughes C.M., Coyne-Johnson L., Whizin N., Oswald K., Shoemaker R., Swanson T., Legasse A.W., Chiuchiolo M.J., Parks C.L., Axthelm M.K., Nelson J.A., Jarvis M.A., Piatak M J.r., Lifson J.D, & Picker L.J. (2011). Profound early control of highly pathogenic SIV by an effector-memory T cell vaccine. Nature, 473(7348), 523-527.

Publication 2011

Acquired Immunodeficiency Syndrome Autopsy BLOOD CD8-Positive T-Lymphocytes Cells Cloning Vectors Cytokine Dental Plaque DNA Replication Flow Cytometry Genes, Reporter Infection Luciferases Macaca mulatta Males Plasma Protoplasm Real-Time Polymerase Chain Reaction Reproduction Reverse Transcriptase Polymerase Chain Reaction Tissues

Most recents protocols related to «Macaca mulatta»

Immunization with Recombinant CD22 Extracellular Domain

Not available on PMC !

Example 2

Immunization with Recombinant Extracellular Domain of CD22.

Twelve UniRat animals (6 HC27, 6 HC28) were immunized with recombinant human CD22 protein. The animals were immunized according to standard protocol using a Titermax/Alhydrogel adjuvant. Recombinant extracellular domain of CD22 was purchased from R&D Systems and was diluted with sterile saline and combined with adjuvant. The immunogen was combined with Titermax and Alhydrogel adjuvants. The first immunization (priming) with immunogen in Titermax was administered in the left and right legs. Subsequent boosting immunizations were done in the presence of Alhydrogel and three days before harvest boosts were performed with immunogens in PBS. Serum was collected from rats at the final bleed to determine serum titers.

Serum Titer Results

Serum titer summary information is shown in FIG. 6. In the graphs depicted in FIG. 6, each line represents an individual animal. The legends of the graphs show the ID number of each individual animal Binding activity for an 8-point dilution series of serum was tested by ELISA against a huCD22+Fc protein, huCD22+His tag, rhesus CD22+His tag protein protein, and a His tag off-target protein. Among this group of animals, a range of serum reactivity levels to both human and rhesus CD22 protein was observed. A serum response to the His protein tag was also observed.

US11873336B2. Heavy chain antibodies binding to CD22 (2024-01-16). TeneoBio, Inc. [US]. Inventors: Shelley Force Aldred [US], Wim van Schooten [US], Heather Anne N. Ogana [US], Laura Marie Davison [US], Katherine Harris [US], Udaya Rangaswamy [US], Nathan D. Trinklein [US].

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Patent 2024

Alhydrogel Animals Antigens CD22 protein, human Enzyme-Linked Immunosorbent Assay Homo sapiens Immunization Leg Macaca mulatta Pharmaceutical Adjuvants Proteins Protein Targeting, Cellular Rattus norvegicus Saline Solution Serum Staphylococcal Protein A Sterility, Reproductive Technique, Dilution TiterMax Vaccination Vaccines, Recombinant

Immunotherapy for Solid Tumors

Not available on PMC !

Example 7

Use in Patients for Treating Solid Tumours

Stored haematopoietic cells (e.g. haematopoietic stem cells or granulocyte precursor cells obtainable therefrom), and granulocytes (e.g. neutrophils) differentiated therefrom are matched to cancer patients based on their cancer type, blood type (ABO, rhesus and HLA), and/or genetics. Patients may also be matched based on human leukocyte antigen (HLA) similarity.

Patients are treated using:

- IV infusion of haematopoietic cells (including haematopoietic stem cells, and granulocyte precursor cells) together with granulocyte-colony stimulating factor, human growth hormone, serotonin, and interleukin into the patient; or
- IV infusion of stimulated granulocyte precursor cells (obtainable from haematopoietic stem cells) into the patient. Without wishing to be bound by theory, it is believed that said cells naturally differentiate into granulocytes (e.g. neutrophils) having a high CKA in a CKA assay in vivo; or
- direct IV infusion of granulocytes (e.g. neutrophils) having a high CKA in a CKA assay which have been differentiated from haematopoietic cells (e.g. haematopoietic stem cells).

Typically, cells are infused once weekly for 8 weeks with a cell volume of 2×10¹¹administered per week. Progress of the therapy is monitored and dosing is adapted accordingly.

US11878033B2. Cancer-killing cells (2024-01-23). LIFT BIOSCIENCES LTD [GB]. Inventors: Alex Blyth [GB], Nico Bruyniks [GB].

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Patent 2024

Biological Assay Cells Granulocyte Granulocyte Colony-Stimulating Factor Granulocyte Precursor Cells Hematopoietic System Histocompatibility Antigens Class II Human Growth Hormone Interleukins Intravenous Infusion Macaca mulatta Malignant Neoplasms Neoplasms Neutrophil Patients Serotonin Stem Cells, Hematopoietic Therapeutics

RNA-seq Data Processing and Variant Calling

RNA-seq data were processed using a uniform pipeline. First, we investigated RNA-seq data quality using FastQC (https://www.bioinformatics.babraham.ac.uk/projects/fastqc/). We removed Illumina adapters and poor quality reads (reads < 36 bp long, leading or trailing reads < Phred score of 3 and allowing a maximum of 2 mismatches per read) using Trimmomatic (version 0.39)^{19 (link)}. Then, we aligned trimmed reads to either the human hg19 genome or the Rhesus Macaque mmul_10 genome using STAR aligner version 2.5.3.a^{20 (link)}. We followed the guidelines outlined by leafcutter (https://davidaknowles.github.io/leafcutter) to align RNA-seq reads and prepare data for differential splicing analyses. RNA-seq read alignment yielded an average of 78,955,738 paired-end reads in humans (s.d. = 29,804,777; M_Alignment = 86.16%; M_{read_size} = 188.36) and a mean of 34,551,920 paired–end reads in primates (s.d. = 8,202,258; M_Alignment = 79.71%; M_{read_size} = 127.59).
DNA genotypes from human RNA-seq data were ascertained via the SAMtools mpileup function as done previously^{21 (link)}. Human genotypes derived from RNA-seq data were phased and imputed with Beagle version 5.1, which uses a probabilistic Hidden Markov Chain model that performs well for sequencing data with sparse genomic coverage^{22 (link)}. We would like to caution the reader that Beagle was originally developed for genome-wide DNA variant data and not RNA-sequencing data. Our analyses used a few methods and criteria for quality control (QC) including: genotyping rate > 95%, minor allele frequency > 0.10, Hardy–Weinberg equilibrium > 1e-6, > 5 reads per sample, Phred Score > 20 and an imputation score > 0.3. The input for imputation was 40,878 called genotypes that were common among all samples and passed initial QC. These variants were imputed to 1000 Genomes Phase III all data, which resulted in 570,755 SNPs, 178,598 of which passed QC. These ~ 170 k variants were used for polygenic score and sQTL analyses. Note, that the 91.9% of these SNPs were present in the AUD GWAS, but that GWAS has 77.9 times more SNPs than the current study. Thus, we encourage the reader to use caution in interpreting our polygenic score and sQTL analyses given the limited number of individuals and the number of SNPs used.

Huggett S.B., Ikeda A.S., Yuan Q., Benca-Bachman C.E, & Palmer R.H. (2023). Genome- and transcriptome-wide splicing associations with alcohol use disorder. Scientific Reports, 13, 3950.

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Publication 2023

Genome Genome, Human Genome-Wide Association Study Genotype Homo sapiens Macaca mulatta Primates RNA-Seq Single Nucleotide Polymorphism

Evaluation of COVID-19 Booster Vaccines in NHPs

Animal experiments were carried out in compliance with all pertinent US National Institutes of Health regulations and were conducted with approved animal protocols from the Institutional Animal Care and Use Committee (IACUC) at the research facilities. NHP studies were conducted at the University of Louisiana at Lafayette New Iberia Research Center.
Two cohorts of vaccinated NHPs received a booster immunization after randomizing each group within a cohort based on their baseline characteristics (Fig. 1).
In the mRNA-primed cohort, six adult male and six adult female Mauritius cynomolgus macaques (Macaca fascicularis) aged 4–10 years, selected based on their responses to the primary vaccination, were randomly allocated to three groups of four animals according to their baseline characteristics.
In the subunit-primed cohort, 15 adult male Indian rhesus macaques (Macaca mulatta) aged 4–7 years were randomly allocated to three groups of five animals. In the priming phase, animals received two immunizations of either Sanofi’s mRNA COVID (ancestral D614) experimental candidate vaccines or CoV2 preS dTM-AS03 (ancestral D614) vaccine through the intramuscular route in the deltoid at day 0 and day 21. Seven months after the primary immunization, both cohorts were immunized with CoV2 preS dTM (ancestral)–AS03, CoV2 preS dTM (Beta)–AS03, and a bivalent CoV2 preS dTM (ancestral + Beta)–AS03. All groups received a total dose of 5 µg of CoV2 preS dTM antigen. All immunologic analyses were performed blinded on serum collected at 7, 14, 21, 28, 56, 84 days, and 6 months post-boost injection for D614G and Beta seroneutralizations; on D14, 56, 84, and 6 months for Delta; on D14 and 6 months for Omicron (BA.1), Omicron BA.4/5, and SARS-CoV1. Animal studies were conducted in compliance with all relevant local, state, and federal regulations, and were approved by the New Iberia Research Center.

Pavot V., Berry C., Kishko M., Anosova N.G., Li L., Tibbitts T., Huang D., Raillard A., Gautheron S., Gutzeit C., Koutsoukos M., Chicz R.M, & Lecouturier V. (2023). Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates. Nature Communications, 14, 1309.

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Publication 2023

Adult Animals Antigens Immunization Institutional Animal Care and Use Committees Macaca fascicularis Macaca mulatta Males Muscles, Deltoid Pressure Protein Subunits RNA, Messenger Secondary Immunization Serum Severe Acute Respiratory Syndrome Vaccination Vaccines Woman

Water-Soluble DREADD Agonist CNO Protocol

To avoid the use of the toxic solvent dimethyl sulfoxide (DMSO), which is typically used for the preparation of CNO products in concentrations of up to 15% (Campbell and Marchant, 2018 (link)), we opted for the use of a water-soluble salt preparation of CNO, CNO dihydrochloride (Tocris, Bio-Techne LTD, Abingdon, UK, catalog no.: 6329) dissolved in sterile saline. The dihydrochloride preparation of CNO undergoes less back-metabolism to clozapine but has a higher bioavailability compared to CNO-DMSO as indicated by pharmacokinetic work in rhesus macaques (Allen et al., 2019 (link)). This product has previously been used in sleep studies on mice at concentrations between 1 and 5 mg/kg (Fernandez et al., 2018 (link); Stucynski et al., 2021 (link)). For C21 injections we used the water-soluble version of DREADD agonist C21 (C21 dihydrochloride, Tocris, Bio-Techne LTD, Abingdon, UK, catalog no.: HB6124). We chose a dose of 3 mg/kg because a detailed pharmacokinetic assessment of this product at this specific concentration as well as behavioural testing in a five-choice serial-reaction-time task did not reveal any behavioural effects at this dose (Jendryka et al., 2019 (link)).

Traut J., Mengual J.P., Meijer E.J., McKillop L.E., Alfonsa H., Hoerder-Suabedissen A., Song S.H., Fehér K.D., Riemann D., Molnar Z., Akerman C.J., Vyazovskiy V.V, & Krone L.B. (2023). Effects of clozapine-N-oxide and compound 21 on sleep in laboratory mice. eLife, 12, e84740.

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Publication 2023

Clozapine Macaca mulatta Metabolism Mice, House Polysomnography Saline Solution Sodium Chloride Solvents Sterility, Reproductive Sulfoxide, Dimethyl

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Monkey chow by Purina

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What are some common challenges researchers face when working with Macaca mulatta?

Researchers working with Macaca mulatta often encounter challenges related to the complex social dynamics and behaviors of these primates. Establishing appropriate housing and handling protocols is critical to ensure the well-being of the animals and the quality of the research data. Additionally, the genetic similarity between Macaca mulatta and humans can complicate study design and data interpretation, requiring careful consideration of potential confounding factors.

How can PubCompare.ai help optimize Macaca mulatta research?

PubCompare.ai is a powerful AI-driven tool that can greatly assist researchers in their Macaca mulatta studies. By allowing you to efficiently screen and compare protocol literature, the platform helps identify the most effective and reproducible methods. The AI-powered analysis provided by PubCompare.ai can highlight critical insights, such as key differences in protocol effectiveness, enabling you to choose the best approach for your specific research goals and enhance the accuracy and reliability of your Macaca mulatta experiments.

Are there different variations or types of Macaca mulatta that researchers should be aware of?

Yes, there are several recognized subspecies and geographic variations of Macaca mulatta. The most commonly studied are the Indian rhesus macaque (M. m. mulatta) and the Chinese rhesus macaque (M. m. tcheliensis). These subspecies can exhibit slight differences in physical characteristics, behavior, and even genetic profiles. Researchers working with Macaca mulatta should be mindful of these variations and ensure that the specific subtype they are using is appropriate for their research objectives and can be accurately compared to existing literature.

What are some of the key applications of Macaca mulatta in biomedical research?

Macaca mulatta has been extensively utilized as a nonhuman primate model in a wide range of biomedical research areas. These include neuroscience, where Macaca mulatta studies have provided insights into brain function and neurological disorders. In immunology, Macaca mulatta has been instrumental in advancing our understanding of the immune system and the development of vaccines and therapeutics. Additionally, Macaca mulatta has been a valuable model in developmental biology, contributing to our knowledge of human growth and development. The genetic similarity between Macaca mulatta and humans makes it a highly relevant model for translating research findings to human health and disease.

How can researchers ensure the quality and reproducibility of their Macaca mulatta studies?

Ensuring the quality and reproducibility of Macaca mulatta studies is crucial for meaningful research outcomes. One key aspect is the selection and optimization of experimental protocols. PubCompare.ai can be an invaluable tool in this regard, as it allows researchers to efficiently screen and compare protocol literature, leveraging AI-driven analysis to identify the most effective and reproducible methods. By utilizing PubCompare.ai, researchers can make informed decisions about the best protocols to use, enhancing the accuracy and reliability of their Macaca mulatta experiments and taking their studies to the next lavel.

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