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1.
Curr Opin Psychol ; 46: 101332, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35367750

RESUMEN

People seek meaning in the marketplace, but can meaning be bought? We review emerging evidence and suggest that the typical association between meaning and well-being is weakened in consumption contexts. We outline two lay beliefs that help explain this gap: the belief that purchases are extrinsic pursuits whereas meaning should come from intrinsic pursuits, and the belief that purchases are impure sources of meaning because companies profit at the expense of people. This conceptual model suggests three paths to enhance meaning and well-being through consumption: reframe purchases as intrinsically rewarding, change (erroneous) lay theories that profit necessarily comes at the expense of the social good, or highlight the future, enduring benefits of consumption.

2.
J Immunol Res ; 2021: 5318590, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34840989

RESUMEN

Nonhuman primates are frequently transported to a new location or temporarily relocated within their colony. Both transportation and relocation expose animals to new environments, causing them to undergo a stress response (before adapting). In our NHP colony, the mentioned situations are not infrequent for many reasons, including maintenance. The objective of this study was to determine whether abrupt changes consisting of relocation, housing, separation, and grouping could influence hematological and immunological parameters and thereby functional activity. The current study used squirrel monkeys as a model to investigate the stress-inducing effects of relocation within a facility, while animals acclimated to new situations (physical, housing). A detailed blood analysis revealed significant changes in lymphocytes, triglycerides, total protein, creatinine, and ALT. Flow cytometric analysis of peripheral blood showed reduction in CD3+, CD4+, and CD8+ T cells and monocytes, while B cells and natural killer (NK) cells changed with relocation. Simultaneously, changes in functional activity of immune cells altered proliferative responses and as shown by ELISpot (IFN γ). Though the parameters studied are not affected as severely as those in animals transported by road or air, stress responses induced by intrafacility relocation are significant and worth consideration. Our findings indicate that squirrel monkeys mimic the features seen in humans exposed to social stressors and may serve an important model for understanding the mechanisms of stress-induced immune dysfunction in humans.


Asunto(s)
Adaptación Fisiológica/inmunología , Linfocitos/inmunología , Estrés Psicológico/inmunología , Animales , Conducta Animal , Células Cultivadas , Modelos Animales de Enfermedad , Ensayo de Immunospot Ligado a Enzimas , Citometría de Flujo , Inestabilidad de Vivienda , Humanos , Interferón gamma/metabolismo , Saimiri , Transportes
3.
Brain ; 144(7): 2146-2165, 2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34128045

RESUMEN

Alzheimer's disease is the most common cause of dementia and the only illness among the top 10 causes of death for which there is no disease-modifying therapy. The failure rate of clinical trials is very high, in part due to the premature translation of successful results in transgenic mouse models to patients. Extensive evidence suggests that dysregulation of innate immunity and microglia/macrophages plays a key role in Alzheimer's disease pathogenesis. Activated resident microglia and peripheral macrophages can display protective or detrimental phenotypes depending on the stimulus and environment. Toll-like receptors (TLRs) are a family of innate immune regulators known to play an important role in governing the phenotypic status of microglia. We have shown in multiple transgenic Alzheimer's disease mouse models that harnessing innate immunity via TLR9 agonist CpG oligodeoxynucleotides (ODNs) modulates age-related defects associated with immune cells and safely reduces amyloid plaques, oligomeric amyloid-ß, tau pathology, and cerebral amyloid angiopathy (CAA) while promoting cognitive benefits. In the current study we have used a non-human primate model of sporadic Alzheimer's disease pathology that develops extensive CAA-elderly squirrel monkeys. The major complications in current immunotherapeutic trials for Alzheimer's disease are amyloid-related imaging abnormalities, which are linked to the presence and extent of CAA; hence, the prominence of CAA in elderly squirrel monkeys makes them a valuable model for studying the safety of the CpG ODN-based concept of immunomodulation. We demonstrate that long-term use of Class B CpG ODN 2006 induces a favourable degree of innate immunity stimulation without producing excessive or sustained inflammation, resulting in efficient amelioration of both CAA and tau Alzheimer's disease-related pathologies in association with behavioural improvements and in the absence of microhaemorrhages in aged elderly squirrel monkeys. CpG ODN 2006 has been well established in numerous human trials for a variety of diseases. The present evidence together with our earlier, extensive preclinical research, validates the beneficial therapeutic outcomes and safety of this innovative immunomodulatory approach, increasing the likelihood of CpG ODN therapeutic efficacy in future clinical trials.


Asunto(s)
Enfermedad de Alzheimer/patología , Encéfalo/patología , Inmunidad Innata/efectos de los fármacos , Oligodesoxirribonucleótidos/farmacología , Envejecimiento/patología , Enfermedad de Alzheimer/inmunología , Péptidos beta-Amiloides/inmunología , Péptidos beta-Amiloides/metabolismo , Animales , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Encéfalo/efectos de los fármacos , Angiopatía Amiloide Cerebral/patología , Femenino , Inmunidad Innata/inmunología , Oligodesoxirribonucleótidos/inmunología , Saimiri , Receptor Toll-Like 9/agonistas , Proteínas tau/metabolismo
4.
PLoS One ; 16(2): e0240705, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33635869

RESUMEN

In the present study, we have quantified the effects of transport, relocation and acclimate/adapt to their new surroundings on female squirrel monkey. These responses are measured in blood samples obtained from squirrel monkeys, at different time points relative to their relocation from their old home to their new home. A group of squirrel monkeys we transported, by truck, for approximately 10 hours. Peripheral blood mononuclear cells (PBMCs) were assayed in order to evaluate the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of cytokines at various time points including immediately before transport, immediately upon arrival, and after approximately 150 days of acclimation. We observed significant changes in T cells and subsets, NK and B cells (CD4+, CD8+, CD4+/CD8+, CD16+, and CD20+). Mitogen specific (e.g. PHA, PWM and LPS) proliferation responses, IFN-γ by ELISPOT assay, and cytokines (IL-2, IL-4 and VEGF) significant changes were observed. Changes seen in the serum chemistry measurements mostly complement those seen in the hematology data. The specific goal was to empirically assess the effects of relocation stress in squirrel monkeys in terms of changes in the numbers and functions of various leukocyte subsets in the blood and the amount of time required for acclimating to their new environment. Such data will help to determine when newly arrived animals become available for use in research studies.


Asunto(s)
Aclimatación/inmunología , Saimiri/inmunología , Estrés Fisiológico/inmunología , Crianza de Animales Domésticos/métodos , Animales , Antígenos CD20 , Linfocitos B , Citocinas/sangre , Femenino , Leucocitos Mononucleares/clasificación , Recuento de Linfocitos/métodos , Subgrupos Linfocitarios/clasificación , Mitógenos , Fenotipo , Saimiri/fisiología , Suero/química , Estrés Fisiológico/fisiología , Linfocitos T , Transportes/métodos
5.
Front Aging Neurosci ; 12: 36, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32194391

RESUMEN

One means of stimulating the mammalian innate immune system is via Toll-like receptor 9 (TLR9) being exposed to unmethylated cytosine-phosphate-guanine (CpG) DNA, also known as pathogen-associated molecular patterns (PAMPs) of microbial origin. Synthetic CpG oligodeoxynucleotides (ODNs) with defined CpG motifs possess broad immunostimulatory properties that make CpG ODNs suitable as therapeutic interventions in a variety of human disease conditions, including Alzheimer's disease (AD). Rodent models are often used to preclinically test the effectiveness of CpG ODN therapeutic agents for AD and other disorders. However, the translatability of findings in such models is limited due to the significant difference of the expression of TLR9 between primates and rodents. The squirrel monkey (SQM), a New World non-human primate (NHP), is known to be phylogenetically proximate to humans, and develops extensive age-dependent cerebral amyloid angiopathy (CAA), a key pathological feature of AD. Hence, this model is currently being used to test AD therapeutics. In the present study, we conducted the first examination of Class C CpG ODN's immunomodulatory role in elderly SQMs. We documented the effectiveness of CpG ODN to trigger an immune response in an aged cohort whose immune system is senescent. The specific immune response patterns detected here closely resembled CpG ODN-induced immunostimulatory patterns observed in prior human studies. Overall, our findings provide critical data regarding the immunomodulatory potential of CpG ODN in this NHP model, allowing for future translational studies of innate immunity stimulation via TLR9 agonists for diverse indications, including AD therapeutics.

6.
Dev Psychobiol ; 62(7): 909-919, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32072635

RESUMEN

Nursery rearing has well-known consequences for primate species. Relative to some other primate species, research has indicated a reduced impact of nursery rearing on squirrel monkeys, particularly in terms of rates, severity, and persistence of abnormal behavior. We administered the Primate Neonatal Neurobehavioral Assessment to 29 dam-reared and 13 nursery-reared squirrel monkeys (Saimiri boliviensis boliviensis) at 2 and 6 weeks of age. Mixed-model ANOVAs comparing composite scores and individual assessment items across age, rearing status, and sex revealed a number of developmental differences. Dam-reared infants scored higher on all four composite measures compared to nursery-reared infants (p < .05) indicating that nursery-reared animals had slower motor development, were less active and attentive, and were more passive than their dam-reared counterparts. Consistent with infant rhesus macaques, nursery-reared squirrel monkeys showed an increased sensitivity to tactile stimulation (p < .05). Altogether, these results suggest a disruption of species-typical development when squirrel monkey infants are reared in a nursery setting, with activity, orientation, and state control areas most affected, though experimental research is needed to determine if this is a causal relationship. Contrary to previous behavioral research, there are likely developmental differences between dam-reared infant squirrel monkeys and those reared in a nursery setting.


Asunto(s)
Animales Recién Nacidos/psicología , Saimiri/psicología , Medio Social , Factores de Edad , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Femenino , Masculino , Pruebas Neuropsicológicas , Saimiri/crecimiento & desarrollo
7.
Comp Med ; 70(2): 160-169, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32014083

RESUMEN

Olive baboons (P. anubis) have provided a useful model of human diseases and conditions, including cardiac, respiratory, and infectious diseases; diabetes; and involving genetics, immunology, aging, and xenotransplantation. The development of a immunologically defined SPF baboons has advanced research further, especially for studies involving the immune system and immunosuppression. In this study, we compare normal immunologic changes of PBMC subsets, and their function in age-matched conventional and SPF baboons. Our results revealed that both groups have comparable numbers of different lymphocyte subsets, but phenotypic differences in central and effector memory T-cell subsets are more pronounced in CD4+ T cells. Despite equal proportions of CD3+ T cells among the conventional and SPF baboons, PBMC from the conventional group showed greater proliferative responses to phytohemagglutinin and pokeweed mitogen and higher numbers of IFNγ-producing cells after stimulation with concanavalin A or pokeweed mitogen, whereas plasma levels of the inflammatory cytokine TNFα were significantly higher in SPF baboons. Exposure of PBMC from conventional baboons to various Toll-like (TLR) ligands, including TLR3, TLR4, and TLR8, yielded increased numbers of IFNγ producing cells, whereas PBMC from SPF baboons stimulated with TLR5 or TLR6 ligand had more IFNγ-producing cells. These findings suggest that although lymphocyte subsets share many phenotypic and functional similarities in conventional and SPF baboons, specific differences in the immune function of lymphocytes could differentially influence the quality and quantity of their innate and adaptive immune responses. These differences should be considered in interpreting experimental outcomes, specifically in studies measuring immunologic endpoints.


Asunto(s)
Inmunidad Celular/inmunología , Enfermedades de los Monos/inmunología , Animales , Femenino , Masculino , Papio , Papio anubis , Linfocitos T/inmunología
8.
Am J Primatol ; 82(11): e23048, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31502301

RESUMEN

Squirrel monkeys are a long-standing biomedical model, with multiple species and subspecies housed in research facilities. Few studies have examined the developmental differences between these subspecies, which may affect research outcomes. The primate neonatal neurobehavioral assessment was completed at 2 weeks of age with 279 dam-reared squirrel monkeys (188 Saimiri boliviensis boliviensis, 45 S. b. peruviensis, and 46 Saimiri. sciureus sciureus). Activity, orientation to stimuli, state control, and motor maturity scores, as well as startle responses and number of vocalizations were compared across subspecies and sex using factorial analysis of covariance (ANCOVAs) controlling for birthweight. There were no differences in orientation or motor maturity scores (p > .05) among the three subspecies or between sexes; however, there were significant subspecies differences in motor activity and state control scores. Of the three subspecies, S. s. sciureus has the lowest state control and activity scores (p < .05). They also had the most exaggerated startle response/aversion to a sudden loud noise, vocalized significantly less, and were less likely to resist restraint during the assessment (p < .05). The three subspecies of squirrel monkeys did not differ in motor development and attention to external stimuli but were significantly different in state control and activity levels. Overall S. s. sciureus were less active, agitated, irritable, and easier to console compared to S. b. boliviensis and S. b. peruviensis. This supports field research on socioecology which documented different social structure and behavior in wild populations of S. s. sciureus compared to S. b. boliviensis and S. b. peruviensis.


Asunto(s)
Animales Recién Nacidos/fisiología , Conducta Animal/fisiología , Saimiri/fisiología , Animales , Femenino , Masculino , Actividad Motora , Pruebas Neuropsicológicas , Reflejo de Sobresalto , Saimiri/crecimiento & desarrollo , Vocalización Animal
9.
J Am Assoc Lab Anim Sci ; 58(6): 774-782, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31604484

RESUMEN

NHP are a small, but critical, portion of the animals studied in research laboratories. Many NHP are imported or raised at one facility and subsequently moved to another facility for research purposes. To improve our understanding of the effects of transportation and relocation on the NHP immune system, to minimize potential confounds associated with relocation, and to maximize study validity, we examined the phenotype and function of PBMC in cynomolgus macaques (Macaca fascicularis) that were transported approximately 200 miles by road from one facility to another. We evaluated the phenotype of lymphocyte subsets through flow cytometry, mitogen-specific immune responses of PBMC in vitro, and plasma levels of circulating cytokines before transportation, at approximately 24 h after arrival (day 2), and after 30 d of acclimation. Analyses of blood samples revealed that the CD3+ and CD4+ T-cell counts increased significantly, whereas NK+, NKT, and CD14+ CD16+ nonclassical monocyte subsets were decreased significantly on day 2 after relocation compared with baseline. We also noted significantly increased immune cell function as indicated by mitogen-specific proliferative responses and by IFNγ levels on day 2 compared with baseline. After 30 d of acclimation, peripheral blood CD4+ T-cells and monocyte counts were higher than baseline, whereas B-cell numbers were lower. The mitogen-induced responses to LPS and IFNγ production after stimulation with pokeweed mitogen or phytohemagglutinin remained significantly different from baseline. In conclusion, the effects of transportation and relocation on immune parameters in cynomolgus monkeys are significant and do not fully return to baseline values even after 30 d of acclimation.


Asunto(s)
Citocinas/metabolismo , Macaca fascicularis/fisiología , Subgrupos de Linfocitos T/fisiología , Transportes , Aclimatación , Crianza de Animales Domésticos , Animales , Ciencia de los Animales de Laboratorio , Macaca fascicularis/inmunología
10.
Am J Primatol ; 81(7): e23026, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31287186

RESUMEN

The weekend effect hypothesis proposes that captive primates are more likely to give birth during times of low disturbance and reduced staff activity. The hypothesis specifically predicts that laboratory-housed primates will be more likely to give birth during the weekend than weekdays when staff activity is reduced. To date, support for the weekend effect hypothesis has been mixed and based on studies with relatively few subjects. To further examine the hypothesis, we analyzed the birthing patterns of three genera of laboratory-housed primates: squirrel monkeys (Saimiri species, N = 2,090 births), owl monkeys (Aotus species, N = 479 births), and rhesus macaques (Macaca mulatta, N = 2,047 births). Contrary to predictions derived from the weekend effect hypothesis, the frequencies of births during weekends for all taxa were not significantly different from rates that would be expected by chance. However, while there was no variance across days of the week, all three taxa gave birth at nighttime, when staff was absent. This parallels reports of births in wild and captive monkeys, both diurnal and nocturnal, which are more likely to give birth during the night; plausibly a time when the environmental and social disturbance is lowest and the mother is safest to bond with her newborn infant. As all births occurred at night, we also explored the relationship between the lunar cycle and the timing of births timing. While the diurnal primates (i.e., Saimiri and Macaca) were no more likely to give birth on "bright" nights than "dark" nights, owl monkeys (Aotus) had a much higher frequency of births on bright nights than darker ones, and at rates that deviated from chance. Our data provide a more detailed understanding on how the environment may influence captive monkey births but do not support the oft-cited weekend effect hypothesis.


Asunto(s)
Animales de Laboratorio/fisiología , Luna , Parto/fisiología , Primates/fisiología , Crianza de Animales Domésticos , Animales , Aotidae/fisiología , Femenino , Macaca mulatta/fisiología , Saimiri/fisiología , Factores de Tiempo
11.
Anim Behav Cogn ; 6(1): 32-47, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32055674

RESUMEN

Games from experimental economics have provided insights into the evolutionary roots of social decision making in primates and other species. Multiple primate species' abilities to cooperate, coordinate and anti-coordinate have been tested utilizing variants of these simple games. Past research, however, has focused on species known to cooperate and coordinate in the wild. To begin to address the degree to which cooperation and coordination may be a general ability that manifests in specific contexts, the present study assessed the decisions of squirrel monkeys (Saimiri boliviensis; N = 10), a species not known for their cooperative behavior in these games. Pairs of monkeys were presented with the Assurance Game (a coordination game), the Hawk-Dove Game (an anti-coordination game) and the Prisoner's Dilemma (a cooperation game with a temptation to defect). We then compared squirrel monkeys' performance to existing data on capuchin monkeys (Sapajus [Cebus] apella), a closely related species that routinely cooperates, to determine what, if any, differences in decision making emerged. Some pairs of both species found the payoff-dominant Nash Equilibrium (NE) in the coordination game, but failed to find the NE in subsequent games. Our results suggest that, like capuchins, squirrel monkeys coordinate their behavior with others, suggesting that such mutual outcomes occur in at least some contexts, even in species that do not routinely cooperate.

12.
PLoS One ; 13(12): e0209391, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30571742

RESUMEN

A strain of Zika virus (ZIKV) of Asian origin associated with birth defects and neurological disorders has emerged and spread through the Americas. ZIKV was first isolated in the blood of nonhuman primates in Africa and has been detected in the blood, saliva, and urine of a few catarrhine species in both Africa and Asia, suggesting that nonhuman primates may serve as both a source and a reservoir of the virus. The recent introduction of ZIKV to human populations in the Americas presents the potential for the virus to spread into nonhuman primate reservoirs. Thus, it is critical to develop efficient and noninvasive detection methods to monitor the spread of the virus in wild nonhuman primate populations. Here, we describe a method for ZIKV detection in noninvasively collected fecal samples of a Neotropical primate. Fecal samples were collected from two captive squirrel monkeys (Saimiri boliviensis boliviensis) that were experimentally infected with ZIKV (Strain Mexico_1_44) and an additional two uninfected squirrel monkeys. Nucleic acids were extracted from these samples, and RT-qPCR was used to assay for the presence of ZIKV using primers flanking a 101 bp region of the NS5 gene. In both ZIKV-inoculated animals, ZIKV was detected 5-11 days post-infection, but was not detected in the uninfected animals. We compare the fecal results to ZIKV detection in serum, saliva, and urine samples from the same individuals. Our results indicate that fecal detection is a cost-effective, noninvasive method for monitoring wild populations of Neotropical primates as possible ZIKV reservoirs.


Asunto(s)
Reservorios de Enfermedades/virología , Heces/virología , ARN Viral/aislamiento & purificación , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Animales , Modelos Animales de Enfermedad , Monitoreo del Ambiente/métodos , Femenino , Humanos , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Saimiri/virología , Saliva/virología , Proteínas no Estructurales Virales/genética , Virus Zika/genética , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/veterinaria , Infección por el Virus Zika/virología
13.
PLoS One ; 13(11): e0198497, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30412580

RESUMEN

Cellular immune responses were tested to determine the effect of fenbendazole on the function of lymphocytes from Bolivian squirrel monkeys (Samiri boliviensis boliviensis). Giardia-infected squirrel monkeys were treated with commercially available fenbendazole (FBZ)-medicated monkey chow. Immune responses were compared between historical controls (Giardia naïve, untreated with FBZ (control animals)) and Giardia-infected, FBZ-treated squirrel monkeys (study animals). Peripheral blood lymphocytes from study monkeys had significantly lower stimulation indices compared to control animals when cultured in vitro with concanavalin A (Con A) (p<0.0001), phytohaemagglutinin (PHA) (p<0.0001) and lipopolysaccharide (LPS) (p<0.0001). PBMCs were also analyzed for IFN-γ producing cells in response to stimulation with Con A, PHA, PWM, and LPS by the cytokine ELISPOT assay. Significantly higher responses to Con A- (p<0.0001), and PHA- (p<0.001) stimulated cultures from Giardia-infected and fenbendazole treated compared to controls. Flow cytometric analysis for expression of cell surface markers revealed a significant increase in B- and NKT-lymphocytes and significant decrease in CD14+CD16+ monocytes after FBZ treatment. Also, circulating plasma cytokines IFN-γ, TNF-α, IL-12p40, IL-1ß, IL-10, IL-13, IL-1ra, IL-6 and IL-4 were significantly decreased after FBZ treatment. Comparison of hematologic parameters between controls and FBZ-treated squirrel monkeys revealed significantly lower numbers of total leukocytes, neutrophils, monocytes, and eosinophils compared to controls. However, erythrocyte indices (red cell count, hemoglobin and hematocrit were significantly higher in FBZ-treated monkeys. Our findings suggest that fenbendazole treatment may alter sensitive immune and molecular measures of inflammation. Postponing the experimental use of squirrel monkeys until at least 6 weeks after FBZ treatment should be considered.


Asunto(s)
Antinematodos/uso terapéutico , Fenbendazol/uso terapéutico , Giardiasis/veterinaria , Inmunidad Celular/efectos de los fármacos , Linfocitos/efectos de los fármacos , Sciuridae/inmunología , Animales , Antinematodos/farmacología , Citocinas/sangre , Fenbendazol/farmacología , Giardiasis/tratamiento farmacológico , Giardiasis/inmunología , Linfocitos/inmunología
14.
Curr Biol ; 28(19): 3193-3197.e5, 2018 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-30270182

RESUMEN

Mutation rates vary between species across several orders of magnitude, with larger organisms having the highest per-generation mutation rates. Hypotheses for this pattern typically invoke physiological or population-genetic constraints imposed on the molecular machinery preventing mutations [1]. However, continuing germline cell division in multicellular eukaryotes means that organisms with longer generation times and of larger size will leave more mutations to their offspring simply as a byproduct of their increased lifespan [2, 3]. Here, we deeply sequence the genomes of 30 owl monkeys (Aotus nancymaae) from six multi-generation pedigrees to demonstrate that paternal age is the major factor determining the number of de novo mutations in this species. We find that owl monkeys have an average mutation rate of 0.81 × 10-8 per site per generation, roughly 32% lower than the estimate in humans. Based on a simple model of reproductive longevity that does not require any changes to the mutational machinery, we show that this is the expected mutation rate in owl monkeys. We further demonstrate that our model predicts species-specific mutation rates in other primates, including study-specific mutation rates in humans based on the average paternal age. Our results suggest that variation in life history traits alone can explain variation in the per-generation mutation rate among primates, and perhaps among a wide range of multicellular organisms.


Asunto(s)
Aptitud Genética/genética , Longevidad/genética , Tasa de Mutación , Animales , Aotidae/genética , Genética de Población/métodos , Genoma/genética , Humanos , Mutación , Linaje , Densidad de Población , Primates/genética , Reproducción
15.
Genes Cancer ; 9(3-4): 142-152, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30108684

RESUMEN

Colorectal cancer accounts for a substantial number of deaths each year worldwide. Lynch Syndrome is a genetic form of colorectal cancer (CRC) caused by inherited mutations in DNA mismatch repair (MMR) genes. Although researchers have developed mouse models of Lynch Syndrome through targeted mutagenesis of MMR genes, the tumors that result differ in important ways from those in Lynch Syndrome patients. We identified 60 cases of CRC in rhesus macaques (Macaca mulatta) at our facility since 2001. The tumors occur at the ileocecal junction, cecum and proximal colon and display clinicopathologic features similar to human Lynch Syndrome. We conducted immunohistochemical analysis of CRC tumors from several rhesus macaques, finding they frequently lack expression of MLH1 and PMS2 proteins, both critical MMR proteins involved in Lynch Syndrome. We also found that most macaque cases we tested exhibit microsatellite instability, a defining feature of Lynch Syndrome. Whole genome sequencing of rhesus macaque CRC cases identified mutations in MLH1 and/or MSH6 that are predicted to disrupt protein function. We conclude that this population of rhesus macaques constitutes a spontaneous model of Lynch Syndrome, matching the human disease in several significant characteristics, including genetic risk factors that parallel human Lynch Syndrome.

16.
Am J Phys Anthropol ; 166(4): 884-894, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29719049

RESUMEN

OBJECTIVES: Sexual selection has seemingly influenced chemical communication in numerous non-human primates, although it is unclear whether it has influenced strictly pair-living and pair-bonded taxa. The physical similarities between male and female owl monkeys suggest that disruptive selection has not played a role in this taxon. However, given their nocturnality, olfactory traits may show differing patterns of sexual selection than visual traits. If sexual selection has influenced chemical communication in owl monkeys, we expect larger scent glands and greater scent-marking in females given the high degree of paternal care, as has been proposed for callitrichines. MATERIALS AND METHODS: We evaluated sex differences in the qualitative and quantitative descriptions of the subcaudal and perianal glandular regions of captive male (n = 39) and female (n = 36) owl monkeys (A. nancymaae), and in the olfactory behaviors performed within breeding pairs (n = 16). RESULTS: Males had larger areas of secretion retained in the hairs covering the subcaudal gland, and females had more and darker secretion than males covering the perianal region. Males inspected the genital region of their partners more frequently than females did, but the sexes did not differ much in other investigative and marking behaviors. DISCUSSION: The observed sex differences and variation in olfactory traits are consistent with the hypothesis that sexual selection has influenced chemical communication in owl monkeys, with males having larger subcaudal glands and spending more time investigating odors. Still, sex differences in monogamous owl monkeys were less extreme than those in other, non-monogamous, taxa.


Asunto(s)
Aotidae/fisiología , Apareamiento , Glándulas Odoríferas/fisiología , Olfato/fisiología , Animales , Antropología Física , Conducta Animal/fisiología , Secreciones Corporales/fisiología , Femenino , Masculino , Caracteres Sexuales
17.
Proc Natl Acad Sci U S A ; 115(11): 2806-2811, 2018 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-29490919

RESUMEN

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.


Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/veterinaria , Macaca mulatta , Homólogo 1 de la Proteína MutL/metabolismo , Enfermedades de los Primates/metabolismo , Animales , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico por imagen , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/metabolismo , Femenino , Macaca mulatta/genética , Macaca mulatta/metabolismo , Masculino , Inestabilidad de Microsatélites , Homólogo 1 de la Proteína MutL/genética , Polimorfismo de Nucleótido Simple , Tomografía Computarizada por Tomografía de Emisión de Positrones , Enfermedades de los Primates/diagnóstico por imagen , Enfermedades de los Primates/genética , Enfermedades de los Primates/patología
18.
Am J Primatol ; 80(2)2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29473987

RESUMEN

Broadening our knowledge of olfactory communication in strictly monogamous systems can inform our understanding of how chemosignals may facilitate social and reproductive behavior between the sexes. Compared to other social and mating systems, relatively little is known about olfactory communication in strictly monogamous non-human primates. Furthermore, platyrrhines are not well represented in chemical analyses of glandular secretions. We conducted semi-quantitative headspace gas chromatography with mass spectrometry to investigate the chemical components of glandular secretions from the subcaudal and pectoral glands of a strictly pair-living platyrrhine, the owl monkey (Aotus spp.). In this study, the first chemical analysis of a wild platyrrhine population, our goals were to (1) conduct a robust analysis of glandular secretions from both captive and wild owl monkey populations and (2) identify whether biologically relevant traits are present in glandular secretions. We also compared and contrasted the results between two Aotus species in different environmental contexts: wild Aotus azarae (N = 33) and captive A. nancymaae (N = 104). Our findings indicate that secretions from both populations encode sex, gland of origin, and possibly individual identity. These consistent patterns across species and contexts suggest that secretions may function as chemosignals. Our data also show that wild A. azarae individuals are chemically discriminated by age (adult or subadult). Among the captive A. nanycmaae, we found chemical differences associated with location, possibly caused by dietary differences. However, there was no noticeable effect of contraception on the chemical profiles of females, nor evidence that closely related individuals exhibit more similar chemical profiles in A. nancymaae. Overall, our data suggest that glandular secretions of both wild and captive Aotus convey specific information. Future studies should use behavioral bioassays to evaluate the ability of owl monkeys to detect signals, and consider whether odor may ultimately facilitate social and sexual relationships between male and female owl monkeys.


Asunto(s)
Aotidae/fisiología , Feromonas/química , Glándulas Odoríferas/metabolismo , Factores de Edad , Comunicación Animal , Animales , Argentina , Secreciones Corporales/química , Secreciones Corporales/metabolismo , Ecosistema , Femenino , Cromatografía de Gases y Espectrometría de Masas/veterinaria , Masculino , Feromonas/metabolismo , Factores Sexuales , Olfato
19.
Am J Trop Med Hyg ; 98(1): 173-177, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29182145

RESUMEN

The establishment of a sylvatic reservoir of Zika virus (ZIKV) in the Americas is dependent on the susceptibility of primates of sufficient population density, the duration and magnitude of viremia, and their exposure to the human mosquito-borne transmission cycle. To assess the susceptibility of squirrel (Saimiri sp.) and owl monkeys (Aotus sp.) to infection, we inoculated four animals of each species with ZIKV from the current epidemic. Viremia in the absence of detectible disease was observed in both species and seroconversion occurred by day 28. ZIKV was detected in the spleen of three owl monkeys: one at 7 days postinoculation (dpi) and two at 14 dpi. This study confirms the susceptibility to ZIKV infection of two Neotropical primate species that live in close proximity to humans in South America, suggesting that they could support a widespread sylvatic ZIKV cycle there. Collectively, establishment of a ZIKV sylvatic transmission cycle in South America would imperil eradication efforts and could provide a mechanism for continued exposure of humans to ZIKV infection and disease.


Asunto(s)
Aotidae/virología , Enfermedades de los Primates/virología , Saimiri/virología , Infección por el Virus Zika/veterinaria , Virus Zika , Animales , Susceptibilidad a Enfermedades/veterinaria , Susceptibilidad a Enfermedades/virología , Femenino , Masculino , Carga Viral/veterinaria , Viremia/veterinaria , Viremia/virología
20.
PLoS One ; 12(12): e0188694, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29261698

RESUMEN

Nonhuman primates from domestic sources constitute a small, but critical, proportion of animals studied in research laboratories. Many of these nonhuman primates are raised at one facility and subsequently transported/relocated to another facility for research purposes. We examined the effects of transport, relocation, and acclimation on the phenotype and function of peripheral blood mononuclear cells (PBMCs) in a group of rhesus monkeys that were transported by road for approximately 21 hours from one facility to another. Using a panel of human antibodies and a set of standardized human immune assays, we evaluated the phenotype of lymphocyte subsets by flow, mitogen-specific immune responses of PBMCs in vitro, and levels of circulating cytokines and cortisol in plasma at various time points including immediately before transport, immediately upon arrival, and after approximately 30 days of acclimation. Analyses of blood samples revealed that CD3+ T-cell and CD20+ B-cell populations had decreased significantly immediately after relocation but had recovered within 30 days after arrival at the new facility. Similarly, circulating cortisol and cytokine levels in plasma were significantly higher immediately after relocation; and by the 30-day time point, these differences were no longer significant. However, immune assays of PBMCs indicated that mitogen-specific responses for proliferation, interferon γ (IFN-γ), and perforin were significantly higher after relocation and 30 days of acclimation. These findings have implications on the research participation of transported and relocated nonhuman primates in immunologic research studies, suggesting that 30 days is not sufficient to ensure return to baseline immune homeostasis. These data should be considered when planning research studies in order to minimize potential confounding factors associated with relocation and to maximize study validity.


Asunto(s)
Aclimatación , Linfocitos/fisiología , Transportes , Animales , Biomarcadores/metabolismo , Proliferación Celular/efectos de los fármacos , Citocinas/sangre , Ensayo de Immunospot Ligado a Enzimas , Femenino , Hidrocortisona/sangre , Interferón gamma/metabolismo , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/fisiología , Linfocitos/efectos de los fármacos , Macaca mulatta , Masculino , Mitógenos/farmacología , Perforina/metabolismo , Fenotipo
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