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result(s) for
"Montague, Michael J."
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Natural disaster and immunological aging in a nonhuman primate
by
Brent, Lauren J. N.
,
Montague, Michael J.
,
Watowich, Marina M.
in
Age Factors
,
Aging
,
Aging (natural)
2022
Weather-related disasters are increasing in frequency and severity, leaving survivors to cope with ensuing mental, financial, and physical hardships. This adversity can exacerbate existing morbidities, trigger new ones, and increase the risk of mortality—features that are also characteristic of advanced age—inviting the hypothesis that extreme weather events may accelerate aging. To test this idea, we examined the impact of Hurricane Maria and its aftermath on immune cell gene expression in large, age-matched, cross-sectional samples from free-ranging rhesus macaques (Macaca mulatta) living on an isolated island. A cross section of macaques was sampled 1 to 4 y before (n = 435) and 1 y after (n = 108) the hurricane. Hurricane Maria was significantly associated with differential expression of 4% of immune-cell-expressed genes, and these effects were correlated with age-associated alterations in gene expression. We further found that individuals exposed to the hurricane had a gene expression profile that was, on average, 1.96 y older than individuals that were not—roughly equivalent to an increase in 7 to 8 y of a human life. Living through an intense hurricane and its aftermath was associated with expression of key immune genes, dysregulated proteostasis networks, and greater expression of inflammatory immune cell-specific marker genes. Together, our findings illuminate potential mechanisms through which the adversity unleashed by extreme weather and potentially other natural disasters might become biologically embedded, accelerate age-related molecular immune phenotypes, and ultimately contribute to earlier onset of disease and death.
Journal Article
Genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies disease models
2024
Understanding and treating human diseases require valid animal models. Leveraging the genetic diversity in rhesus macaque populations across eight primate centers in the United States, we conduct targeted-sequencing on 1845 individuals for 374 genes linked to inherited human retinal and neurodevelopmental diseases. We identify over 47,000 single nucleotide variants, a substantial proportion of which are shared with human populations. By combining rhesus and human allele frequencies with established variant prediction methods, we develop a machine learning-based score that outperforms established methods in predicting missense variant pathogenicity. Remarkably, we find a marked number of loss-of-function variants and putative deleterious variants, which may lead to the development of rhesus disease models. Through phenotyping of macaques carrying a pathogenic OPA1:p.A8S variant, we identify a genetic model of autosomal dominant optic atrophy. Finally, we present a public website housing variant and genotype data from over two thousand rhesus macaques.
This study on the genetic diversity of 1,845 rhesus macaques improves genetic variation interpretation and identifies macaque models for inherited human retinal and neurodevelopment diseases.
Journal Article
Age and sex-associated variation in the multi-site microbiome of an entire social group of free-ranging rhesus macaques
by
Janiak, Mareike C.
,
Stock, Michala K.
,
Villamil, Catalina I.
in
Aging
,
Animal models
,
Animals
2021
Background
An individual’s microbiome changes over the course of its lifetime, especially during infancy, and again in old age. Confounding factors such as diet and healthcare make it difficult to disentangle the interactions between age, health, and microbial changes in humans. Animal models present an excellent opportunity to study age- and sex-linked variation in the microbiome, but captivity is known to influence animal microbial abundance and composition, while studies of free-ranging animals are typically limited to studies of the fecal microbiome using samples collected non-invasively. Here, we analyze a large dataset of oral, rectal, and genital swabs collected from 105 free-ranging rhesus macaques (
Macaca mulatta
, aged 1 month-26 years), comprising one entire social group, from the island of Cayo Santiago, Puerto Rico. We sequenced 16S V4 rRNA amplicons for all samples.
Results
Infant gut microbial communities had significantly higher relative abundances of
Bifidobacterium
and
Bacteroides
and lower abundances of
Ruminococcus
,
Fibrobacter
, and
Treponema
compared to older age groups, consistent with a diet high in milk rather than solid foods. The genital microbiome varied widely between males and females in beta-diversity, taxonomic composition, and predicted functional profiles. Interestingly, only penile, but not vaginal, microbiomes exhibited distinct age-related changes in microbial beta-diversity, taxonomic composition, and predicted functions. Oral microbiome composition was associated with age, and was most distinctive between infants and other age classes.
Conclusions
Across all three body regions, with notable exceptions in the penile microbiome, while infants were distinctly different from other age groups, microbiomes of adults were relatively invariant, even in advanced age. While vaginal microbiomes were exceptionally stable, penile microbiomes were quite variable, especially at the onset of reproductive age. Relative invariance among adults, including elderly individuals, is contrary to findings in humans and mice. We discuss potential explanations for this observation, including that age-related microbiome variation seen in humans may be related to changes in diet and lifestyle.
4_dARqKdohA9mAZyu7q9YN
Video abstract
Journal Article
SIV infection induces alterations in gene expression and loss of interneurons in Rhesus Macaque frontal cortex during early systemic infection
by
Hayes, Matthew R.
,
Kolson, Dennis L.
,
Divakaran, Saurabh S.
in
631/208/212/748
,
631/378/340
,
Animals
2025
Understanding the neurobiological mechanisms underlying HIV-associated neurocognitive decline in people living with HIV is frequently complicated by an inability to analyze changes across the course of the infection and frequent presence of comorbid psychiatric and substance use disorders. Preclinical non-human primate simian immunodeficiency virus (SIV) models help address these shortcomings. However, SIV studies frequently target protracted endpoints, limiting our understanding of the neuromolecular alterations during the early post-infection window. To begin to address this knowledge gap, we utilized single nuclei transcriptomics to examine frontal cortex samples of rhesus macaques 10- and 20-days post-SIV infection, compared to non-infected controls. We identify and validated a decrease in inhibitory neurons during the early post infection window, representing a potential substrate of longer-term injury and neurocognitive impairment in people living with HIV. Differential expression identified alterations in cellular subtype gene expression that persisted over the 20-day time course and short-lived differences only detected at 10-days post-SIV infection. In silico predicted regulatory mechanisms and dysregulated neural signaling pathways are presented. Analysis of cell-cell interaction networks identify altered signal pathways in the frontal cortex that may represent regional alterations in cell-cell communications. In total, these results identify cell type-specific molecular mechanisms putatively capable of underlying long-term neurocognitive alterations in persons living with HIV.
Journal Article
Genome sequence of the basal haplorrhine primate Tarsius syrichta reveals unusual insertions
by
Rozhdestvensky, Timofey
,
Wilson, Richard K.
,
Clawson, Hiram
in
631/208/182
,
631/208/212/2304
,
631/208/726/2001
2016
Tarsiers are phylogenetically located between the most basal strepsirrhines and the most derived anthropoid primates. While they share morphological features with both groups, they also possess uncommon primate characteristics, rendering their evolutionary history somewhat obscure. To investigate the molecular basis of such attributes, we present here a new genome assembly of the Philippine tarsier (
Tarsius syrichta
), and provide extended analyses of the genome and detailed history of transposable element insertion events. We describe the silencing of
Alu
monomers on the lineage leading to anthropoids, and recognize an unexpected abundance of long terminal repeat-derived and LINE1-mobilized transposed elements (
Tarsius
interspersed elements; TINEs). For the first time in mammals, we identify a complete mitochondrial genome insertion within the nuclear genome, then reveal tarsier-specific, positive gene selection and posit population size changes over time. The genomic resources and analyses presented here will aid efforts to more fully understand the ancient characteristics of primate genomes.
Tarsiers occupy a key node between strepsirrhines and anthropoids in the primate phylogeny. Here, Warren and colleagues present the genome of
Tarsius syrichta
, including a survey of transposable elements, an unusual mitochondrial insertion, and evidence for positive gene selection.
Journal Article
The ocular surface microbiome of rhesus macaques
by
Martinez, Melween I.
,
Hass, Joelle K.
,
Brent, Lauren J. N.
in
Agriculture
,
Amplicon sequencing
,
Animal models
2025
Background
The ocular surface microbiota (OSM) is important for eye health, and variations in OSM composition have been associated with multiple diseases in humans. Studies of OSM-disease dynamics in humans are confounded by lifestyle factors. Animal models provide a complementary approach to understanding biological systems, free from many confounds of human studies. Here, we provide the first study of the OSM of rhesus macaques, a premier animal model for eye health and disease. We describe the taxonomy of the rhesus macaque OSM, and explore compositional correlations with age, sex, and living condition.
Methods
We analyzed eyelid and conjunctival microbiota swabs from 132 individual rhesus macaques (
Macaca mulatta
) (57 males, 75 females, 1–26 years old) from one captive and one free-ranging group using 16 S rRNA V3/V4 MiSeq sequencing. We investigated alpha diversity, beta diversity, and differential abundance.
Results
We found several similarities between the top Phyla and Genera of the rhesus macaque OSM and those reported in human literature. Significantly higher alpha diversity, which may reflect age-related ocular surface mucous membrane integrity and immune function, was present in younger individuals compared to older ones. Higher alpha diversity was also present in free-ranging rhesus macaques compared to ones in captivity, possibly related to differences in diet, exercise, and medical exposures between macaques in different living conditions. Beta diversity was most strongly influenced by individual identity, followed by living conditions. Sex did not correlate with any OSM variation.
Conclusions
In this study we describe the taxonomic composition of the rhesus macaque OSM, and identify significant differences in alpha and beta diversity according to individual nonhuman primate host variables and the surrounding environment. Our findings suggest composition of the nonhuman primate OSM is shaped by age-related physiology, individual identity, and external living conditions. Our results offer novel insights into an underexplored region of the primate microbiome and highlight the utility of rhesus macaques as a model system for investigating the links between the OSM, ocular health, and disease.
Journal Article
Color vision and niche partitioning in a diverse neotropical primate community in lowland Amazonian Ecuador
2021
A recent focus in community ecology has been on how within‐species variability shapes interspecific niche partitioning. Primate color vision offers a rich system in which to explore this issue. Most neotropical primates exhibit intraspecific variation in color vision due to allelic variation at the middle‐to‐long‐wavelength opsin gene on the X chromosome. Studies of opsin polymorphisms have typically sampled primates from different sites, limiting the ability to relate this genetic diversity to niche partitioning. We surveyed genetic variation in color vision of five primate species, belonging to all three families of the primate infraorder Platyrrhini, found in the Yasuní Biosphere Reserve in Ecuador. The frugivorous spider monkeys and woolly monkeys (Ateles belzebuth and Lagothrix lagotricha poeppigii, family Atelidae) each had two opsin alleles, and more than 75% of individuals carried the longest‐wavelength (553–556 nm) allele. Among the other species, Saimiri sciureus macrodon (family Cebidae) and Pithecia aequatorialis (family Pitheciidae) had three alleles, while Plecturocebus discolor (family Pitheciidae) had four alleles—the largest number yet identified in a wild population of titi monkeys. For all three non‐atelid species, the middle‐wavelength (545 nm) allele was the most common. Overall, we identified genetic evidence of fourteen different visual phenotypes—seven types of dichromats and seven trichromats—among the five sympatric taxa. The differences we found suggest that interspecific competition among primates may influence intraspecific frequencies of opsin alleles. The diversity we describe invites detailed study of foraging behavior of different vision phenotypes to learn how they may contribute to niche partitioning. Neotropical primates exhibit substantial variation within and between species in color vision abilities; however, little work has explored interspecific variation in a single primate community. In this study, we genotyped functional variation in the middle‐to‐long‐wavelength opsin gene in populations of five sympatric primate species at the Yasuní Biosphere Reserve in Ecuador. We found substantial interspecific and intraspecific variation in color vision across the five species and discuss our findings in the context of dietary specialization and niche partitioning.
Journal Article
Rhesus macaques as a tractable physiological model of human ageing
by
Sterner, Kirstin N.
,
Goldman, Elisabeth A.
,
Horvath, Julie E.
in
Aging
,
Animals
,
Gene Regulatory Networks - immunology
2020
Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from short-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research owing to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with the model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population. This article is part of the theme issue ‘Evolution of the primate ageing process’.
Journal Article
Whole genome analysis of a schistosomiasis-transmitting freshwater snail
2017
Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis
Journal Article