Publications by authors named "Leah A Owens"

11 Publications

  • Page 1 of 1

A Sarcina bacterium linked to lethal disease in sanctuary chimpanzees in Sierra Leone.

Nat Commun 2021 02 3;12(1):763. Epub 2021 Feb 3.

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.

Human and animal infections with bacteria of the genus Sarcina (family Clostridiaceae) are associated with gastric dilation and emphysematous gastritis. However, the potential roles of sarcinae as commensals or pathogens remain unclear. Here, we investigate a lethal disease of unknown etiology that affects sanctuary chimpanzees (Pan troglodytes verus) in Sierra Leone. The disease, which we have named "epizootic neurologic and gastroenteric syndrome" (ENGS), is characterized by neurologic and gastrointestinal signs and results in death of the animals, even after medical treatment. Using a case-control study design, we show that ENGS is strongly associated with Sarcina infection. The microorganism is distinct from Sarcina ventriculi and other known members of its genus, based on bacterial morphology and growth characteristics. Whole-genome sequencing confirms this distinction and reveals the presence of genetic features that may account for the unusual virulence of the bacterium. Therefore, we propose that this organism be considered the representative of a new species, named "Candidatus Sarcina troglodytae". Our results suggest that a heretofore unrecognized complex of related sarcinae likely exists, some of which may be highly virulent. However, the potential role of "Ca. S. troglodytae" in the etiology of ENGS, alone or in combination with other factors, remains a topic for future research.
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http://dx.doi.org/10.1038/s41467-021-21012-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859188PMC
February 2021

Age Patterning in Wild Chimpanzee Gut Microbiota Diversity Reveals Differences from Humans in Early Life.

Curr Biol 2021 02 23;31(3):613-620.e3. Epub 2020 Nov 23.

Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA. Electronic address:

Survival in primates is facilitated by commensal gut microbes that ferment otherwise indigestible plant matter, resist colonization by pathogens, and train the developing immune system. However, humans are unique among primates in that we consume highly digestible foods, wean early, mature slowly, and exhibit high lifelong investments in maintenance. These adaptations suggest that lifetime trajectories of human-microbial relationships could differ from those of our closest living relatives. Here, we profile the gut microbiota of 166 wild chimpanzees aged 8 months to 67 years in the Kibale National Park, Uganda and compare the patterns of gut microbial maturation to those previously observed in humans. We found that chimpanzee gut microbial alpha-diversity, composition, density, interindividual variation, and within-individual change over time varied significantly with age. Notably, gut microbial signatures in infants <2 years old were distinct across all five metrics. Infant chimpanzee guts were enriched in some of the same taxa prevalent in infant humans (e.g., Bifidobacterium, Streptococcus, and Bacteroides), and chimpanzee gut microbial communities, like those of humans, exhibited higher interindividual variation in infancy versus later in life. However, in direct contrast to human infants, chimpanzee infants harbored surprisingly high-diversity rather than low-diversity gut bacterial communities compared with older conspecifics. These data indicate differential trajectories of gut microbiota development in humans and chimpanzees that are consistent with interspecific differences in lactation, diet, and immune function. Probing the phenotypic consequences of differential early-life gut microbial diversity in chimpanzees and other primates will illuminate the life history impacts of the hominid-microbiome partnership.
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http://dx.doi.org/10.1016/j.cub.2020.10.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993011PMC
February 2021

Demography, life-history trade-offs, and the gastrointestinal virome of wild chimpanzees.

Philos Trans R Soc Lond B Biol Sci 2020 11 21;375(1811):20190613. Epub 2020 Sep 21.

University of Wisconsin-Madison, Madison, WI 53706, USA.

In humans, senescence increases susceptibility to viral infection. However, comparative data on viral infection in free-living non-human primates-even in our closest living relatives, chimpanzees and bonobos ( and )-are relatively scarce, thereby constraining an evolutionary understanding of age-related patterns of viral infection. We investigated a population of wild eastern chimpanzees (), using metagenomics to characterize viromes (full viral communities) in the faeces of 42 sexually mature chimpanzees (22 males, 20 females) from the Kanyawara and Ngogo communities of Kibale National Park, Uganda. We identified 12 viruses from at least four viral families possessing genomes of both single-stranded RNA and single-stranded DNA. Faecal viromes of both sexes varied with chimpanzee age, but viral richness increased with age only in males. This effect was largely due to three viruses, salivirus, porprismacovirus and chimpanzee stool-associated RNA virus (chisavirus), which occurred most frequently in samples from older males. This finding is consistent with the hypothesis that selection on males for early-life reproduction compromises investment in somatic maintenance, which has delayed consequences for health later in life, in this case reflected in viral infection and/or shedding. Faecal viromes are therefore useful for studying processes related to the divergent reproductive strategies of males and females, ageing, and sex differences in longevity. This article is part of the theme issue 'Evolution of the primate ageing process'.
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http://dx.doi.org/10.1098/rstb.2019.0613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540950PMC
November 2020

Simultaneous outbreaks of respiratory disease in wild chimpanzees caused by distinct viruses of human origin.

Emerg Microbes Infect 2019 ;8(1):139-149

e University of Wisconsin-Madison , Madison , WI , USA.

Respiratory viruses of human origin infect wild apes across Africa, sometimes lethally. Here we report simultaneous outbreaks of two distinct human respiratory viruses, human metapneumovirus (MPV; Pneumoviridae: Metapneumovirus) and human respirovirus 3 (HRV3; Paramyxoviridae; Respirovirus, formerly known as parainfluenza virus 3), in two chimpanzee (Pan troglodytes schweinfurthii) communities in the same forest in Uganda in December 2016 and January 2017. The viruses were absent before the outbreaks, but each was present in ill chimpanzees from one community during the outbreak period. Clinical signs and gross pathologic changes in affected chimpanzees closely mirrored symptoms and pathology commonly observed in humans for each virus. Epidemiologic modelling showed that MPV and HRV3 were similarly transmissible (R of 1.27 and 1.48, respectively), but MPV caused 12.2% mortality mainly in infants and older chimpanzees, whereas HRV3 caused no direct mortality. These results are consistent with the higher virulence of MPV than HRV3 in humans, although both MPV and HRV3 cause a significant global disease burden. Both viruses clustered phylogenetically within groups of known human variants, with MPV closely related to a lethal 2009 variant from mountain gorillas (Gorilla beringei beringei), suggesting two independent and simultaneous reverse zoonotic origins, either directly from humans or via intermediary hosts. These findings expand our knowledge of human origin viruses threatening wild chimpanzees and suggest that such viruses might be differentiated by their comparative epidemiological dynamics and pathogenicity in wild apes. Our results also caution against assuming common causation in coincident outbreaks.
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http://dx.doi.org/10.1080/22221751.2018.1563456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455141PMC
July 2019

Ambient urban dust particulate matter reduces pathologic T cells in the CNS and severity of EAE.

Environ Res 2019 01 1;168:178-192. Epub 2018 Oct 1.

Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA. Electronic address:

Background: Autoimmune diseases have increased in incidence and prevalence worldwide. While genetic predispositions play a role, environmental factors are a major contributor. Atmospheric particulate matter (PM) is a complex mixture composed of metals, nitrates, sulfates and diverse adsorbed organic compounds like polycyclic aromatic hydrocarbons (PAHs) and dioxins. Exposure to atmospheric PM aggravates autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus, among others. PAHs and dioxins are known aryl hydrocarbon receptor (AHR) ligands. The AHR modulates T cell differentiation and directs the balance between effector and regulatory T cells in vitro and in experimental autoimmune encephalomyelitis (EAE), a murine model of autoimmune disease. This study aims to identify pathways that contribute to autoimmune disease and their potential use as therapeutic targets to alleviate symptoms and the need for global immunosuppression. This study tests the hypothesis that atmospheric PM enhances effector T cell differentiation and aggravates autoimmune disease.

Results: An atmospheric ambient urban dust PM sample, standard reference material (SRM)1649b, was tested for its effects on autoimmunity. SRM1649b PM enhanced Th17 differentiation in an AHR-dependent manner in vitro, however intranasal treatment of SRM1649b PM delayed onset of EAE and reduced cumulative and peak clinical scores. Chronic and acute intranasal exposure of SRM1649b PM delayed onset of EAE. Chronic intranasal exposure did not reduce severity of EAE while acute intranasal exposure significantly reduced severity of disease. Acute intranasal treatment of low dose SRM1649b PM had no effect on clinical score or day of onset in EAE. Delayed onset of EAE by intranasal SRM1649b PM was AHR-dependent in vivo. Oral gavage of SRM1649b PM, in the absence of AHR ligands in the diet, had no effect on day of disease onset or severity of EAE. Day 10 analysis of T cells in the CNS after intranasal treatment of SRM1649b PM showed a reduction of pathologic T cell subsets in vivo. Moreover, MOG-specific splenocytes require AHR to generate or maintain IL-10 producing cells and reduce IFNγ producing cells in vitro.

Conclusions: These results identify the AHR pathway as a potential target for driving targeted immunosuppression in the CNS in the context of atmospheric PM-mediated autoimmune disease. The effects of SRM1649b PM on EAE are dependent on route of exposure, with intranasal treatment reducing severity of EAE and delaying disease onset while oral gavage has no effect. Intranasal SRM1649b PM reduces pathologic T cells in the CNS, specifically Th1 cells and Th1Th17 double positive cells, leading to reduced severity of EAE and AHR-dependent delayed disease onset. Additionally, SRM1649b PM treatment of antigen-specific T cells leads to AHR-dependent increase in percent IL-10 positive cells in vitro. These findings may shed light on the known increase of infection after exposure to atmospheric PM and serve as the first step in identifying components of the AHR pathway responsible for Th1-mediated immunosuppression in response to atmospheric PM exposure.
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http://dx.doi.org/10.1016/j.envres.2018.09.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263800PMC
January 2019

Differential effects of diesel exhaust particles on T cell differentiation and autoimmune disease.

Part Fibre Toxicol 2018 08 24;15(1):35. Epub 2018 Aug 24.

Department of Surgery, Division of Transplantation, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Avenue MC7375, Madison, WI, 53792, USA.

Background: Exposure to particulate matter (PM) has been associated with increased incidence and severity of autoimmune disease. Diesel PM is primarily composed of an elemental carbon core and adsorbed organic compounds such as polycyclic aromatic hydrocarbons (PAHs) and contributes up to 40% of atmospheric PM. The organic fraction (OF) of PM excludes all metals and inorganics and retains most organic compounds, such as PAHs. Both PM and OF increase inflammation in vitro and aggravate autoimmune disease in humans. PAHs are known aryl hydrocarbon receptor (AHR) ligands. The AHR modulates T cell differentiation and effector function in vitro and in experimental autoimmune encephalomyelitis (EAE), a murine model of autoimmune disease. This study aims to identify whether the total mass or active components of PM are responsible for activating pathways associated with exposure to PM and autoimmune disease. This study tests the hypothesis that active components present in diesel PM and their OF enhance effector T cell differentiation and aggravate autoimmune disease.

Results: Two different diesel samples, each characterized for their components, were tested for their effects on autoimmunity. Both diesel PM enhanced effector T cell differentiation in an AHR-dose-dependent manner and suppressed regulatory T cell differentiation in vitro. Both diesel PM aggravated EAE in vivo. Fractionated diesel OFs exhibited the same effects as PM in vitro, but unlike PM, only one diesel OF aggravated EAE. Additionally, both synthetic PAH mixtures that represent specific PAHs found in the two diesel PM samples enhanced Th17 differentiation, however one lost this effect after metabolism and only one required the AHR.

Conclusions: These findings suggest that active components of PM and not total mass are driving T cell responses in vitro, but in vivo the PM matrix and complex mixtures adsorbed to the particles, not just the OF, are contributing to the observed EAE effects. This implies that examining OF alone may not be sufficient in vivo. These data further suggest that bioavailability and metabolism of organics, especially PAHs, may have an important role in vivo.
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http://dx.doi.org/10.1186/s12989-018-0271-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109291PMC
August 2018

A novel mouse model for non-invasive single marker tracking of mammary stem cells in vivo reveals stem cell dynamics throughout pregnancy.

PLoS One 2009 Nov 25;4(11):e8035. Epub 2009 Nov 25.

Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.

Mammary stem cells (MaSCs) play essential roles for the development of the mammary gland and its remodeling during pregnancy. However, the precise localization of MaSCs in the mammary gland and their regulation during pregnancy is unknown. Here we report a transgenic mouse model for luciferase-based single marker detection of MaSCs in vivo that we used to address these issues. Single transgene expressing mammary epithelial cells were shown to reconstitute mammary glands in vivo while immunohistochemical staining identified MaSCs in basal and luminal locations, with preponderance towards the basal position. By quantifying luciferase expression using bioluminescent imaging, we were able to track MaSCs non-invasively in individual mice over time. Using this model to monitor MaSC dynamics throughout pregnancy, we found that MaSCs expand in both total number and percentage during pregnancy and then drop down to or below baseline levels after weaning. However, in a second round of pregnancy, this expansion was not as extensive. These findings validate a powerful system for the analysis of MaSC dynamics in vivo, which will facilitate future characterization of MaSCs during mammary gland development and breast cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008035PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777504PMC
November 2009

Solution NMR structure of the SOS response protein YnzC from Bacillus subtilis.

Proteins 2008 Jul;72(1):526-30

Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.

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http://dx.doi.org/10.1002/prot.22064DOI Listing
July 2008

Inner retinal photoreception independent of the visual retinoid cycle.

Proc Natl Acad Sci U S A 2006 Jul 20;103(27):10426-10431. Epub 2006 Jun 20.

Departments of *Ophthalmology and Visual Sciences and

Mice lacking the visual cycle enzymes RPE65 or lecithin-retinol acyl transferase (Lrat) have pupillary light responses (PLR) that are less sensitive than those of mice with outer retinal degeneration (rd/rd or rdta). Inner retinal photoresponses are mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting that the melanopsin-dependent photocycle utilizes RPE65 and Lrat. To test this hypothesis, we generated rpe65(-/-); rdta and lrat(-/-); rd/rd mutant mice. Unexpectedly, both rpe65(-/-); rdta and lrat(-/-); rd/rd mice demonstrate paradoxically increased PLR photosensitivity compared with mice mutant in visual cycle enzymes alone. Acute pharmacologic inhibition of the visual cycle of melanopsin-deficient mice with all-trans-retinylamine results in a near-total loss of PLR sensitivity, whereas treatment of rd/rd mice has no effect, demonstrating that the inner retina does not require the visual cycle. Treatment of rpe65(-/-); rdta with 9-cis-retinal partially restores PLR sensitivity. Photic sensitivity in P8 rpe65(-/-) and lrat(-/-) ipRGCs is intact as measured by ex vivo multielectrode array recording. These results demonstrate that the melanopsin-dependent ipRGC photocycle is independent of the visual retinoid cycle.
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http://dx.doi.org/10.1073/pnas.0600917103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1502474PMC
July 2006
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