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The 2022 monkeypox virus (MPXV) outbreaks spurred global public health concern. In response, we undertook a living systematic review of its zoonotic characteristics, including potential reservoirs and susceptible species, transmissibility, and clinical presentation in nonhuman species. Electronic database searches yielded 148 eligible records published between 2000 and 2022. Primary reservoirs remain unidentified, with natural isolation identified in 2 species, the sooty mangabey monkey and rope squirrel. Transmission primarily occurs from animals to humans, but evidence of reverse zoonosis has emerged. Data on clinical infection and manifestations are sparse, with evidence of potentially susceptible species drawn primarily from experimental studies. Only 10% of articles were appropriate for quality assessment and most of these were rated as critically low. Overall, while evidence regarding MPXV exists, the quality of data are extremely poor, resulting in significant uncertainty regarding MPXV's zoonotic traits. High-quality empirical research to understand the impact of MPXV on animal and human populations is warranted. [ABSTRACT FROM AUTHOR]

The human otolithic system (utricle and saccule), housed within the bony vestibule of the inner ear, establishes our sense of balance in conjunction with the semicircular canals. Yet, while the morphological evolution of the semicircular canals is actively explored, comparative morphological analyses of the otolithic system are lacking. This is regrettable because functional links with head orientation suggest the otolithic system could be used to track postural change throughout human evolution and across primates more broadly. In this context, we present the first analysis of the evolution of the human otolithic system within an anthropoid primate setting. Using the vestibule as a morphological proxy for the utricle and saccule, we compare humans to 13 other extant anthropoid species, and use phylogenetically-informed methods to find correlations with body size, endocranial flexion, and head-neck posture. Our results, obtained through micro-CT of 136 inner ears, reveal two major evolutionary transitions in hominoids, leading to distinctive vestibular morphology in humans, characterized by otolithic morphology resembling squirrel monkeys (possibly due to reversal), with a pronounced supraovalic fossa. Finally, we find a positional signal embedded in the anthropoid bony vestibule, providing the foundation to further explore the evolution of human head-neck posture using inner ear morphology. Morphometric modeling reveals evolutionary divergences of the otolithic inner ear in humans and apes, with a possible link to the evolution of postural behavior. [ABSTRACT FROM AUTHOR]

Most Plasmodium vivax infections contain genetically distinct parasites, but the consequences of this polyclonality on the development of asexual parasites, their sexual differentiation, and their transmission remain unknown. We describe infections of Saimiri monkeys with two strains of P. vivax and the analyses of 80,024 parasites characterized by single cell RNA sequencing and individually genotyped. In our model, consecutive inoculations fail to establish polyclonal infections. By contrast, simultaneous inoculations of two strains lead to sustained polyclonal infections, although without detectable differences in parasite regulation or sexual commitment. Analyses of sporozoites dissected from mosquitoes fed on coinfected monkeys show that all genotypes are successfully transmitted to mosquitoes. However, after sporozoite inoculation, not all genotypes contribute to the subsequent blood infections, highlighting an important bottleneck during pre-erythrocytic development. Overall, these studies provide new insights on the mechanisms regulating the establishment of polyclonal P. vivax infections and their consequences for disease transmission. Single cell analyses of non-human primates infected with one or two strains of Plasmodium vivax provide insights on the origin of polyclonality in patients and reveal an important population bottleneck occurring during pre-erythrocytic development. [ABSTRACT FROM AUTHOR]

Simple Summary: Mammals nurse their young through rapid early growth. Most placental mammals bridge the period with a set of small, temporary 'deciduous' or 'milk' teeth. At some point, a mother weans her young, who must then feed independently to survive. How tooth eruption integrates with gestation, birth and weaning is explored here for 71 species in nine mammalian orders. Body weights range from 22 g to 4300 kg and maternal investment (gestation plus nursing) ranges from 6 weeks to more than 7 years. These mammals differ widely at birth, from no teeth to all deciduous teeth emerging, but commonalities appear when infants transit to independent feeding. Weaning takes place with an entire deciduous dentition, closest in time to emergence of the first permanent molars and well before second molars emerge. Adult body size explains less about tooth eruption than expected. Instead, many mammals, from monkey to moose, limit maternal investment (from initial pregnancy to young with first molars) to just under one year, timing infant development to annual cycles. Mammals that invest multiple years in their young include several critically endangered species. Integrating tooth emergence into life history gives insight into living mammals and builds a framework for interpreting the fossil record. The young of toothed mammals must have teeth to reach feeding independence. How tooth eruption integrates with gestation, birth and weaning is examined in a life-history perspective for 71 species of placental mammals. Questions developed from high-quality primate data are then addressed in the total sample. Rather than correlation, comparisons focus on equivalence, sequence, the relation to absolutes (six months, one year), the distribution of error and adaptive extremes. These mammals differ widely at birth, from no teeth to all deciduous teeth emerging, but commonalities appear when infants transit to independent feeding. Weaning follows completion of the deciduous dentition, closest in time to emergence of the first permanent molars and well before second molars emerge. Another layer of meaning appears when developmental age is counted from conception because the total time to produce young feeding independently comes up against seasonal boundaries that are costly to cross for reproductive fitness. Mammals of a vast range of sizes and taxa, from squirrel monkey to moose, hold conception-to-first molars in just under one year. Integrating tooth emergence into life history gives insight into living mammals and builds a framework for interpreting the fossil record. [ABSTRACT FROM AUTHOR]

Background: Major histocompatibility complex (MHC) class II molecules expressed on B cells, monocytes and dendritic cells present processed peptides to CD4+ T cells as one of the mechanisms to combat infection and inflammation. Aim: To study MHC II expression in a variety of nonhuman primate species, including New World (NWM) squirrel monkeys (Saimiri boliviensis boliviensis), owl monkeys (Aotus nancymae), common marmosets (Callithrix spp.), and Old World (OWM) rhesus (Macaca mulatta), baboons (Papio anubis). Methods: Two clones of cross‐reactive mouse anti‐human HLADR monoclonal antibodies (mAb) binding were analyzed by flow cytometry to evaluate MHC II expression on NHP immune cells, including T lymphocytes in whole blood (WB) and peripheral blood mononuclear cells (PBMC). Results: MHC class II antibody reactivity is seen with CD20+ B cells, CD14+ monocytes and CD3+ T lymphocytes. Specific reactivity with both clones was demonstrated in T lymphocytes: this reactivity was not inhibited by purified CD16 antibody but was completely inhibited when pre‐blocked with purified unconjugated MHC II antibody. Freshly prepared PBMC also showed reactivity with T lymphocytes without any stimulation. Interestingly, peripheral blood from rhesus macaques and olive baboons (OWM) showed no such T lymphocyte associated MHCII antibody reactivity. Discussion & Conclusion: Our results from antibody (MHC II) reactivity clearly show the potential existence of constitutively expressed (with no stimulation) MHC II molecules on T lymphocytes in new world monkeys. These results suggest that additional study is warranted to evaluate the functional and evolutionary significance of these finding and to better understand MHC II expression on T lymphocytes in new world monkeys. [ABSTRACT FROM AUTHOR]

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Clostridium perfringens is a commensal bacterium of humans and other animals that can become pathogenic, causing myonecrosis and enteric diseases. Previous studies have reported C. perfringens infection in several wild animals as well as its presence as a commensal, but its role in animals of the Amazon region is largely unknown. Thus, this study investigated the occurrence of C. perfringens in samples from wild mammals treated at the Wild Animals Sector of the Veterinary Hospital of the Federal University of Pará in the Amazon biome. The results demonstrate that C. perfringens type A was the only toxinotype isolated from mammals in the Amazon biome, demonstrating the importance of further studies on the topic in wild animals, their impacts and the diseases caused. The objective of this study was to evaluate the occurrence of Clostridium perfringens in stool samples and swabs collected from wild mammals in the Amazon biome. Sixty-five faecal and swab samples were collected in situ and ex situ from 16 species and three genera of wild mammals, some of which were in good health and some of which had diarrhoea. After pre-enrichment, the samples were plated on selective agar for C. perfringens. Characteristic colonies were subjected to multiplex PCR for the detection of genes encoding the main C. perfringens toxins (alpha, beta, epsilon, and iota toxin and enterotoxin). Among the 65 samples, 40 (61.5%) were positive for the gene encoding the alpha toxin and were classified as type A, 36 of which were asymptomatic animals and four were diarrheal. No other toxinotypes were found. The findings of this study suggest that C. perfringens type A is commonly found in mammal species of the Amazon biome. This seems to be the first study to identify C. perfringens type A in species such as B. variegatus (common ground sloth), C. didactylus (two-toed sloth), P. flavus (Jupará), T. tetradactyla (anteater), S. collinsi (squirrel monkey), S. niger (black marmoset), and S. apella (Guyana capuchin) and in the genus Didelphis sp. (opossum). [ABSTRACT FROM AUTHOR]

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic (forest) cycles involving monkeys and canopy-living Aedes mosquitoes. Both viruses spilled over into human transmission and were translocated to the Americas, opening a path for spillback into Neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We infected a native, Asian host species (cynomolgus macaque) and a novel, American host species (squirrel monkey) with sylvatic strains of DENV-2 or ZIKV via mosquito bite. We then monitored aspects of viral replication (viremia), innate and adaptive immune response (natural killer (NK) cells and neutralizing antibodies, respectively), and transmission to mosquitoes. In both hosts, ZIKV reached high titers that translated into high transmission to mosquitoes; in contrast DENV-2 replicated to low levels and, unexpectedly, transmission occurred only when serum viremia was below or near the limit of detection. Our data reveal evidence of an immunologically-mediated trade-off between duration and magnitude of virus replication, as higher peak ZIKV titers are associated with shorter durations of viremia, and higher NK cell levels are associated with lower peak ZIKV titers and lower anti-DENV-2 antibody levels. Furthermore, patterns of transmission of each virus from a Neotropical monkey suggest that ZIKV has greater potential than DENV-2 to establish a sylvatic transmission cycle in the Americas. Hanley et al show that transmission of dengue and Zika virus from Old and New World monkeys is shaped by an immunologically-mediated trade-off between magnitude and duration of replication. Patterns of Zika transmission suggests high risk of spillback into neotropical monkeys. [ABSTRACT FROM AUTHOR]

Nonhuman primates are an important experimental model for the development of targeted biological therapeutics because of their immunological closeness to humans. However, there are very few antibody reagents relevant for delineating the different immune cell subsets based on nonhuman primate antigens directly or with cross-reactivity to those in humans. Here, we report specific expression of HLA-DR, PD-1, and CD123 on different circulating immune cell subsets in the peripheral blood that included T cells (CD3+), T cells subsets (CD4+ and CD8+), B cells (CD20+), natural killer (NK) cells (CD3–CD16+), and natural killer T cells (CD3+CD16+) along with different monocyte subsets in squirrel monkey (Saimiri sciureus). We established cross-reactivity of commercial mouse antihuman monoclonal antibodies (mAbs), with these various immune cell surface markers. These findings should aid further future comprehensive understanding of the immune parameters and identification of new biomarkers to significantly improve SQM as a model for biomedical studies. [ABSTRACT FROM AUTHOR]

Wildlife trafficking creates favorable scenarios for intra- and inter-specific interactions that can lead to parasite spread and disease emergence. Among the fauna affected by this activity, primates are relevant due to their potential to acquire and share zoonoses - infections caused by parasites that can spread between humans and other animals. Though it is known that most primate parasites can affect multiple hosts and that many are zoonotic, comparative studies across different contexts for animal-human interactions are scarce. We conducted a multi-parasite screening targeting the detection of zoonotic infections in wild-caught monkeys in nine Peruvian cities across three contexts: captivity (zoos and rescue centers, n = 187); pet (households, n = 69); and trade (trafficked or recently confiscated, n = 132). We detected 32 parasite taxa including mycobacteria, simian foamyvirus, bacteria, helminths, and protozoa. Monkeys in the trade context had the highest prevalence of hemoparasites (including Plasmodium malariae/brasilianum, Trypanosoma cruzi, and microfilaria) and enteric helminths and protozoa were less common in pet monkeys. However, parasite communities showed overall low variation between the three contexts. Parasite richness (PR) was best explained by host genus and the city where the animal was sampled. Squirrel (genus Saimiri) and wooly (genus Lagothrix) monkeys had the highest PR, which was ~2.2 times the PR found in tufted capuchins (genus Sapajus) and tamarins (genus Saguinus/Leontocebus) in a multivariable model adjusted for context, sex, and age. Our findings illustrate that the threats of wildlife trafficking to One Health encompass exposure to multiple zoonotic parasites well-known to cause disease in humans, monkeys, and other species. We demonstrate these threats continue beyond the markets where wildlife is initially sold; monkeys trafficked for the pet market remain a reservoir for and contribute to the translocation of zoonotic parasites to households and other captive facilities where contact with humans is frequent. Our results have practical applications for the healthcare of rescued monkeys and call for urgent action against wildlife trafficking and ownership of monkeys as pets. [ABSTRACT FROM AUTHOR]

The observation of amyloid-β (Aβ) lesions using autofluorescence in transgenic mice and human Alzheimer disease patients has been reported frequently. However, no reports verify the autofluorescence of spontaneous Aβ amyloidosis in animals, to our knowledge. We validated the autofluorescence of Aβ lesions in spontaneous squirrel monkey cases under label-free conditions; lesions had intense blue-white autofluorescence in fluorescence microscopy using excitation light at 400–440 nm. Thioflavin S staining and immunohistochemistry of the same specimens revealed that this blue-white autofluorescence was derived from Aβ lesions. Hyperspectral analysis of these lesions revealed a characteristic spectrum with bimodal peaks at 440 and 460 nm, as reported for Aβ lesions in mice. Principal component analysis using hyperspectral data specifically separated the Aβ lesions from other autofluorescent substances, such as lipofuscin. A non-labeled and mechanistic detection of Aβ lesions by hyperspectral imaging could provide valuable insights for developing early diagnostic techniques. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation and thick, red, scaly plaques on the skin characterize psoriasis vulgaris, which is a common and varied chronic inflammatory dermatological disorder. IL-26 has been categorized as both an IL-10 family member and an IL-20 subfamily member. This cytokine was first found in T cells that had been modified by the herpesvirus saimiri. Aim of the work: We want to learn more about the relationship between IL-26 levels and the severity of psoriasis by comparing the serum and tissue IL-26 levels of people with psoriasis to those of a healthy control group. Patients and Methods: This study was a case-control research that took place between March 2021 and September 2021 at the Beni-Suef University Hospital Dermatology outpatient clinic. Twenty men and ten females with psoriasis participated in the research, which was approved by the Research Ethics Committee (REC). Patients' ages varied widely, from 28 to 50, with a mean (standard deviation) of (42.50 ±6.5) years. Thirty people who did not have psoriasis (healthy controls) participated in the research. In terms of age and sex, these controls were excellent analogs for the psoriasis patients. Every individual who took part in the study had their whole medical and personal history compiled. The IL-26 Human ELISA kit was used to analyze the concentration of IL-26 in the blood and their expression in tissues. Results: In contrast to the control group of healthy people, those with a psoriasis diagnosis were shown to have significantly higher levels of serum IL-26 and tissue expression. Clinical psoriasis severity, as measured by the Psoriasis Area and Severity Index (PASI) score, was shown to be positively correlated with both the blood level and tissue expression of IL-26. Serum IL-26 concentration was positively and statistically significantly related to Psoriasis disease severity and duration. Serum and tissue levels were not associated with age, gender, family history, onset, or progression of illness in patients. Conclusion: IL-26 may be related to the severity of psoriasis and plays a crucial part in the disease's development. Our research looks at how Interleukin-26 (IL-26) plays a part in the development of psoriasis by analyzing its expression in both tissue and serum samples. [ABSTRACT FROM AUTHOR]

Simple Summary: Glucocorticoids (GCs) play a vital role in the body's response to stress. Therefore, scientists use GC level measurements as a valuable tool to understand the well-being of animals in behavioral, conservation, and welfare research. GC levels can be measured from different sample types, one of them being saliva. Saliva samples are especially useful because they can be collected rather easily and in a non-invasive manner. The aim of this study is to validate a method to measure salivary GCs, i.e., an enzyme immunoassay, in two monkey species: capuchin monkeys and squirrel monkeys. Individuals of both species were trained to provide saliva samples. Using high-pressure liquid chromatography, we confirmed that two main GCs, cortisol, and cortisone, are present in the saliva of these species and that they can be detected by the enzyme immunoassay. We further verified the biological validity of the assay in the two species by showing that it can track the decrease in cortisol levels throughout the day, which is typical in these monkeys. Our findings support the usefulness of the enzyme immunoassay to measure salivary cortisol levels in these non-human primate species and highlight its potential as a valid tool in research and welfare assessment. Glucocorticoids (GCs) are mammalian steroid hormones involved in a variety of physiological processes, including metabolism, the immune response, and cardiovascular functions. Due to their link to the physiological stress response, GC measurement is a valuable tool for conservation and welfare assessment in animal populations. GC levels can be measured from different matrices, such as urine and feces. Moreover, especially in captive settings, measuring GCs from saliva samples proved particularly useful as those samples can be collected non-invasively and easily from trained animals. Salivary GC levels can be measured using a variety of analytical methods, such as enzyme immunoassays. However, it is crucial to validate the analytical method for each specific application and species when using a new matrix. Using high-pressure liquid chromatography and a cortisol enzyme immunoassay, we show that the main glucocorticoids secreted in the saliva of squirrel monkeys and brown capuchin monkeys are cortisol and cortisone. Our biological validation found the expected salivary cortisol level to decline throughout the day. Our findings support the reliability of salivary cortisol measurements and their potential to be used as a valid tool in research and welfare assessment for these non-human primates. [ABSTRACT FROM AUTHOR]

Resting-state fMRI based on analyzing BOLD signals is widely used to derive functional networks in the brain and how they alter during disease or injury conditions. Resting-state networks can also be used to study brain functional connectomes across species, which provides insights into brain evolution. The squirrel monkey (SM) is a non-human primate (NHP) that is widely used as a preclinical model for experimental manipulations to understand the organization and functioning of the brain. We derived resting-state networks from the whole brain of anesthetized SMs using Independent Component Analysis of BOLD acquisitions. We detected 15 anatomically constrained resting-state networks localized in the cortical and subcortical regions as well as in the white-matter. Networks encompassing visual, somatosensory, executive control, sensorimotor, salience and default mode regions, and subcortical networks including the Hippocampus-Amygdala, thalamus, basal-ganglia and brainstem region correspond well with previously detected networks in humans and NHPs. The connectivity pattern between the networks also agrees well with previously reported seed-based resting-state connectivity of SM brain. This study demonstrates that SMs share remarkable homologous network organization with humans and other NHPs, thereby providing strong support for their suitability as a translational animal model for research and additional insight into brain evolution across species. [ABSTRACT FROM AUTHOR]

Platy-1 retroposons are short interspersed elements (SINEs) unique to platyrrhine primates. Discovered in the common marmoset (Callithrix jacchus) genome in 2016, these 100 bp mobile element insertions (MEIs) appeared to be novel drivers of platyrrhine evolution, with over 2200 full-length members across 62 different subfamilies, and strong evidence of ongoing proliferation in C. jacchus. Subsequent characterization of Platy-1 elements in Aotus, Saimiri and Cebus genera, suggested that the widespread mobilization detected in marmoset (family Callithrichidae) was perhaps an anomaly. Two additional Callithrichidae genomes are now available, a scaffold level genome assembly for Saguinus imperator (tamarin; SagImp_v1) and a chromosome-level assembly for Saguinus midas (Midas tamarin; ASM2_v1). Here, we report that each tamarin genome contains over 11,000 full-length Platy-1 insertions, about 1150 are shared by both Saguinus tamarins, 7511 are unique to S. imperator, and another 8187 are unique to S. midas. Roughly 325 are shared among the three callithrichids. We identified six new Platy-1 subfamilies derived from Platy-1-8, with the youngest new subfamily, Platy-1-8c_Saguinus, being the primary source of the Saguinus amplification burst. This constitutes the largest expansion of Platy-1 MEIs reported to date and the most extensive independent SINE amplification between two closely related species. [ABSTRACT FROM AUTHOR]

In the wild, coordinated behaviour across group members is essential for maintaining spatial coherence, with potential implications for individual fitness. Such coordination often leads to behavioural synchrony (performing the same behaviour at the same time). Tufted capuchins (Sapajus apella) and squirrel monkeys (Saimiri sciureus) are known to form mixed-species groups (MSGs), travelling and foraging together. Yet, it is unclear if it is necessary to synchronize behaviours in captivity when ecological pressures are minimal compared to the wild. We investigated the extent to which two MSGs of capuchins (N = 35) and squirrel monkeys (N = 26) synchronized their behaviour with conspecifics and heterospecifics at the Living Links to Human Evolution Research Centre, RZSS, Edinburgh Zoo, UK. Group activities were sampled by instantaneous scans of all visible individuals. Scans (n = 180) were analysed for five most frequently observed behaviours. Intraspecies synchrony was calculated using Simpson's Diversity Index, and interspecies synchrony was measured using cross-correlations. Intraspecific synchrony was significantly greater compared to randomly aggregated data, while cross-correlations indicated interspecific asynchrony. Living together did not lead to interspecific synchrony as may be expected given the coordination and behaviour described in the wild, and shared husbandry in captivity. Overall, our findings highlight differences in the behavioural structure of single- versus MSGs. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'. [ABSTRACT FROM AUTHOR]

Although very well adapted to brain study, Magnetic Resonance Imaging (MRI) remains limited by the facilities and capabilities required to acquire data, especially for non-human primates. Addressing the data gaps resulting from these limitations requires making data more accessible and open. In contempt of the regular use of Saimiri sciureus in neuroscience research, in vivo diffusion has yet to be openly available for this species. Here we built and made openly available a unique new resource consisting of a high-resolution, multishell diffusion-weighted dataset in the anesthetized Saimiri sciureus. The data were acquired on 11 individuals with an 11.7 T MRI scanner (isotropic resolution of 400 µm3). This paper presents an overview of our dataset and illustrates some of its possible use through example analyses. To assess the quality of our data, we analyzed long-range connections (whole-brain tractography), microstructure (Neurite Orientation Dispersion and Density Imaging), and axon diameter in the corpus callosum (ActiveAx). Constituting an essential new resource for primate evolution studies, all data are openly available. [ABSTRACT FROM AUTHOR]

Recovery of motor function after stroke is accompanied by reorganization of movement representations in spared cortical motor regions. It is widely assumed that map reorganization parallels recovery, suggesting a causal relationship. We examined this assumption by measuring changes in motor representations in eight male and six female squirrel monkeys in the first few weeks after injury, a time when motor recovery is most rapid. Maps of movement representations were derived using intracortical microstimulation techniques in primary motor cortex (M1), ventral premotor cortex (PMv), and dorsal premotor cortex (PMd) in 14 adult squirrel monkeys before and after a focal infarct in the M1 distal forelimb area. Maps were derived at baseline and at either 2 (n = 7) or 3 weeks (n = 7) postinfarct. In PMv the forelimb maps remained unchanged at 2 weeks but contracted significantly (242.4%) at 3 weeks. In PMd the forelimb maps expanded significantly (1110.6%) at 2 weeks but contracted significantly (257.4%) at 3 weeks. Motor deficits were equivalent at both time points. These results highlight two features of plasticity after M1 lesions. First, significant contraction of distal forelimb motor maps in both PMv and PMd is evident by 3 weeks. Second, an unpredictable nonlinear pattern of reorganization occurs in the distal forelimb representation in PMd, first expanding at 2 weeks, and then contracting at 3 weeks postinjury. Together with previous results demonstrating reliable map expansions in PMv several weeks to months after M1 injury, the subacute time period may represent a critical window for the timing of therapeutic interventions. [ABSTRACT FROM AUTHOR]

During the Zika virus (ZIKV) outbreak and after evidence of its sexual transmission was obtained, concerns arose about the impact of the adverse effects of ZIKV infection on human fertility. In this study, we evaluated the clinical-laboratory aspects and testicular histopathological patterns of pubertal squirrel monkeys (Saimiri collinsi) infected with ZIKV, analyzing the effects at different stages of infection. The susceptibility of S. collinsi to ZIKV infection was confirmed by laboratory tests, which detected viremia (mean 1.63 × 106 RNA copies/µL) and IgM antibody induction. Reduced fecal testosterone levels, severe testicular atrophy and prolonged orchitis were observed throughout the experiment by ultrasound. At 21 dpi, testicular damage associated with ZIKV was confirmed by histopathological and immunohistochemical (IHC) analyses. Tubular retraction, the degeneration and necrosis of somatic and germ cells in the seminiferous tubules, the proliferation of interstitial cells and an inflammatory infiltrate were observed. ZIKV antigen was identified in the same cells where tissue injuries were observed. In conclusion, squirrel monkeys were found to be susceptible to the Asian variant of ZIKV, and this model enabled the identification of multifocal lesions in the seminiferous tubules of the infected group evaluated. These findings may suggest an impact of ZIKV infection on male fertility. [ABSTRACT FROM AUTHOR]

Between 2016 and 2018, Brazil experienced the largest sylvatic epidemic of yellow fever virus (YFV). Despite to the magnitude and rapid spread of the epidemic, little is known about YFV dispersion. The study evaluated whether the squirrel monkey is a good model for yellow fever (YF) studies. Methods: Ten animals were infected with 1 × 106 PFU/mL of YFV, with one negative control. Blood samples were collected daily during the first 7 days and at 10, 20 and 30 days post infection (dpi) for detection of viral load and cytokines by RT-qPCR; measurements of AST, ALT, urea and creatinine were taken; IgM/IgG antibodies were detected by ELISA, and hemagglutination inhibition and neutralization tests were performed. The animals exhibited fever, flushed appearance, vomiting and petechiae, and one animal died. Viremia was detected between 1 and 10 dpi, and IgM/IgG antibodies appeared between 4 and 30 dpi. The levels of AST, ALT and urea increased. The immune responses were characterized by expression of S100 and CD11b cells; endothelial markers (VCAM-1, ICAM-1 and VLA-4), cell death and stress (Lysozyme and iNOS); and pro-inflammatory cytokines (IL-8, TNF-α, and IFN-γ) and anti-inflammatory cytokines (IL-10 and TGF-β). The squirrel monkeys showed changes similar to those described in humans with YF, and are a good experimental model for the study of YF. [ABSTRACT FROM AUTHOR]

Prosthenorchis elegans is a worm of the family Archiacanthocephala that infects non-human primates in the Americas, producing an intestinal pathology that may compromise the life of its hosts. Squirrel monkeys, Saimiri oerstedii citrinellus, were found with P. elegans in Costa Rica. Histopathological analysis revealed a severe pyogranulomatous response composed by macrophages, neutrophils, eosinophils, fibroblasts and lymphocytes. Morphological worm analyses revealed 36 hooks in the proboscis distributed in six rows; and total body, hook and lemnisci length were compatible to the original descriptions of P. elegans. In addition, phylogenetic, haplotype network and genetic distance analyses were done on cytochrome oxidase subunit 1, cox1, sequences obtained from the collected specimens. Sequences obtained herein clustered separately with high posterior probabilities in a Bayesian Inference tree and showed 8.12% nucleotide differences when compared to P. elegans from Colombia. This high divergence was confirmed in the TCS network that separated Colombian and Costa Rican sequences by 32 mutational steps, a genetic distance PCA which separated sequences from both geographical locations by 89.5% and an FST value of 0.655, indicating the presence of cryptic diversity in P. elegans. Additional studies from specimens collected from other definitive hosts and geographical locations are required to better understand the biodiversity of this species. [ABSTRACT FROM AUTHOR]

Non-human primates contribute to the spread of yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas, such as Brazil. This study aims to investigate virological, histopathological and immunohistochemical findings in livers of squirrel monkeys (Saimiri spp.) infected with the YFV. Viremia occurred 1–30 days post infection (dpi) and the virus showed a predilection for the middle zone (Z2). The livers were jaundiced with subcapsular and hemorrhagic multifocal petechiae. Apoptosis, lytic and coagulative necrosis, steatosis and cellular edema were also observed. The immune response was characterized by the expression of S100, CD11b, CD57, CD4 and CD20; endothelial markers; stress and cell death; pro and anti-inflammatory cytokines, as well as Treg (IL-35) and IL-17 throughout the experimental period. Lesions during the severe phase of the disease were associated with excessive production of apoptotic pro-inflammatory cytokines, such as IFN-γ and TNF-α, released by inflammatory response cells (CD4+ and CD8+ T lymphocytes) and associated with high expression of molecules of adhesion in the inflammatory foci observed in Z2. Immunostaining of the local endothelium in vascular cells and the bile duct was intense, suggesting a fundamental role in liver damage and in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Relationships among the small monkeys living in the Americas such as the squirrel monkeys, owl monkeys (the 'night monkeys'), marmosets and capuchins (the 'organ grinder' monkeys) are still under debate. This study utilized multi-species DNA sequence alignments to investigate these relationships. Each alignment contained a unique Alu element insertion, a genetic marker considered 'identical by descent' such that the absence of the Alu element is the ancestral state. Alu element diversity reveals that the emergence and radiation of these different primate lineages was rapid and complex. The close relationship between squirrel monkey and capuchins was confirmed while the placement of owl monkey with respect to the marmoset remains unresolved. The results of this study will assist in research and conservation strategies for America's monkeys. Phylogenetic relationships among Cebidae species of platyrrhine primates are presently under debate. Studies prior to whole genome sequence (WGS) availability utilizing unidirectional Alu repeats linked Callithrix and Saguinus as sister taxa, based on a limited number of genetic markers and specimens, while the relative positions of Cebus, Saimiri and Aotus remained controversial. Multiple WGS allowed computational detection of Alu-genome junctions, however random mutation and evolutionary decay of these short-read segments prevented phylogenetic resolution. In this study, WGS for four Cebidae genomes of marmoset, squirrel monkey, owl monkey and capuchin were analyzed for full-length Alu elements and each locus was compared to the other three genomes in all possible combinations using orthologous region sequence alignments. Over 2000 candidates were aligned and subjected to visual inspection. Approximately 34% passed inspection and were considered shared in their respective category, 48% failed due to the target being present in all four genomes, having N's in the sequence or other sequence quality anomalies, and 18% were determined to represent near parallel insertions (NP). Wet bench locus specific PCR confirmed the presence of shared Alu insertions in all phylogenetically informative categories, providing evidence of extensive incomplete lineage sorting (ILS) and an abundance of Alu proliferation during the complex radiation of Cebidae taxa. [ABSTRACT FROM AUTHOR]

The platyrrhine family Cebidae (capuchin and squirrel monkeys) exhibit among the largest primate encephalization quotients. Each cebid lineage is also characterized by notable lineage-specific traits, with capuchins showing striking similarities to Hominidae such as high sensorimotor intelligence with tool use, advanced cognitive abilities, and behavioral flexibility. Here, we take a comparative genomics approach, performing genome-wide tests for positive selection across five cebid branches, to gain insight into major periods of cebid adaptive evolution. We uncover candidate targets of selection across cebid evolutionary history that may underlie the emergence of lineage-specific traits. Our analyses highlight shifting and sustained selective pressures on genes related to brain development, longevity, reproduction, and morphology, including evidence for cumulative and diversifying neurobiological adaptations across cebid evolution. In addition to generating a high-quality reference genome assembly for robust capuchins, our results lend to a better understanding of the adaptive diversification of this distinctive primate clade. [ABSTRACT FROM AUTHOR]

Axonal patches are known as the major sites of synaptic connections in the cerebral cortex of higher order mammals. However, the functional role of these patches is highly debated. Patches are formed by populations of nearby neurons in a topographic manner and are recognized as the termination fields of long-distance lateral connections within and between cortical areas. In addition, axons form numerous boutons that lie outside the patches, whose function is also unknown. To better understand the functional roles of these two distinct populations of boutons, we compared individual and collective morphological features of axons within and outside the patches of intraareal, feedforward, and feedback pathways by way of tract tracing in the somatosensory cortex of New World monkeys. We found that, with the exception of tortuosity, which is an invariant property, bouton spacing and axonal convergence properties differ significantly between axons within patch and no-patch domains. Principal component analyses corroborated the clustering of axons according to patch formation without any additional effect by the type of pathway or laminar distribution. Stepwise logistic regression identified convergence and bouton density as the best predictors of patch formation. These findings support that patches are specific sites of axonal convergence that promote the synchronous activity of neuronal populations. On the other hand, nopatch domains could form a neuroanatomical substrate to diversify the responses of cortical neurons. [ABSTRACT FROM AUTHOR]

Herpesvirus saimiri (HVS) is discussed as a possible vector in gene therapy. In order to create a self-repairing HVS vector, the F plasmid vector moiety of the bacterial artificial chromosome (BAC) was transposed via Red recombination into the virus genes ORF22 or ORF29b, both important for virus replication. Repetitive sequences were additionally inserted, allowing the removal of the F-derived sequences from the viral DNA genome upon reconstitution in permissive epithelial cells. Moreover, these self-repair-enabled BACs were used to generate deletion variants of the transforming strain C488 in order to minimalize the virus genome. Using the en passant mutagenesis with two subsequent homologous recombination steps, the BAC was seamlessly manipulated. To ensure the replication capacity in permissive monkey cells, replication kinetics for all generated virus variants were documented. HVS variants with increased insert capacity reached the self-repair within two to three passages in permissive epithelial cells. The seamless deletion of ORFs 3/21, 12–14, 16 or 71 did not abolish replication competence. Apoptosis induction did not seem to be altered in human T cells transformed with deletion variants lacking ORF16 or ORF71. These virus variants form an important step towards creating a potential minimal virus vector for gene therapy, for example, in human T cells. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an emergent, amphixenotic infection that resulted in a pandemic declaration in March 2020. A rapid search for appropriate animal models of this newly emergent viral respiratory disease focused initially on traditional nonhuman primate research species. Nonhuman primate models have previously been shown to be valuable in evaluation of emerging respiratory coronaviruses with pandemic potential (ie, SARS-CoV and Middle East respiratory syndrome coronavirus). In this article, we review the pulmonary histopathologic characteristics and immunohistochemical evaluation of experimental SARS-CoV-2 infection in the rhesus macaque, pigtail macaque, African green monkey, and squirrel monkey. Our results indicate that all evaluated nonhuman primate species developed variably severe histopathologic changes typical of coronavirus respiratory disease characterized by interstitial pneumonia with or without syncytial cell formation, alveolar fibrin, and pulmonary edema that progressed to type II pneumocyte hyperplasia. Lesion distribution was multifocal, frequently subpleural, and often more severe in lower lung lobes. However, squirrel monkeys showed the least severe and least consistent lesions of the evaluated nonhuman primates. Additionally, our results highlight the disparate physical relationship between viral antigen and foci of pulmonary lesions. While classic respiratory coronaviral lesions were observed in the lungs of all nonhuman primates evaluated, none of the primates exhibited severe lesions or evidence of diffuse alveolar damage and therefore are unlikely to represent the severe form of SARS-CoV-2 infection observed in fatal human cases. [ABSTRACT FROM AUTHOR]

Accurate processing and analysis of non-human primate (NHP) brain magnetic resonance imaging (MRI) serves an indispensable role in understanding brain evolution, development, aging, and diseases. Despite the accumulation of diverse NHP brain MRI datasets at various developmental stages and from various imaging sites/scanners, existing computational tools designed for human MRI typically perform poor on NHP data, due to huge differences in brain sizes, morphologies, and imaging appearances across species, sites, and ages, highlighting the imperative for NHP-specialized MRI processing tools. To address this issue, in this paper, we present a robust, generic, and fully automated computational pipeline, called non-human primates Brain Extraction and Segmentation Toolbox (nBEST), whose main functionality includes brain extraction, non-cerebrum removal, and tissue segmentation. Building on cutting-edge deep learning techniques by employing lifelong learning to flexibly integrate data from diverse NHP populations and innovatively constructing 3D U-NeXt architecture, nBEST can well handle structural NHP brain MR images from multi-species, multi-site, and multi-developmental-stage (from neonates to the elderly). We extensively validated nBEST based on, to our knowledge, the largest assemblage dataset in NHP brain studies, encompassing 1,469 scans with 11 species (e.g., rhesus macaques, cynomolgus macaques, chimpanzees, marmosets, squirrel monkeys, etc.) from 23 independent datasets. Compared to alternative tools, nBEST outperforms in precision, applicability, robustness, comprehensiveness, and generalizability, greatly benefiting downstream longitudinal, cross-sectional, and cross-species quantitative analyses. We have made nBEST an open-source toolbox (https://github.com/TaoZhong11/nBEST) and we are committed to its continual refinement through lifelong learning with incoming data to greatly contribute to the research field. • We proposed nBEST, a deep-learning toolbox for processing MR images of non-human primate brains. • nBEST leverages lifelong learning and 3D U-NeXt models, performing brain extraction, non-cerebrum removal, and tissue segmentation. • Validated with 1,400+ scans from 11 species, nBEST shows extensive applicabilit. • nBEST is available online with a user manual. [ABSTRACT FROM AUTHOR]

Retroviruses have left their legacy in host genomes over millions of years as endogenous retroviruses (ERVs), and their structure, diversity, and prevalence provide insights into the historical dynamics of retrovirus-host interactions. In bioinformatic analyses of koala (Phascolarctos cinereus) whole-genome sequences, we identify a recently expanded ERV lineage (phaCin-ß) that is related to the New World squirrel monkey retrovirus. This ERV expansion shares many parallels with the ongoing koala retrovirus (KoRV) invasion of the koala genome, including highly similar and mostly intact sequences, and polymorphic ERV loci in the sampled koala population. The recent phaCin-ß ERV colonization of the koala genome appears to predate the current KoRV invasion, but polymorphic ERVs and divergence comparisons between these two lineages predict a currently uncharacterized, possibly still extant, phaCin-ß retrovirus. The genomics approach to ERV-guided discovery of novel retroviruses in host species provides a strong incentive to search for phaCin-ß retroviruses in the Australasian fauna. [ABSTRACT FROM AUTHOR]

Since the establishment of slave plantations in French Guiana during the 17th century, the small island of Ilet la Mère, located 11 km from Cayenne, has functioned as site of confinement, refuge, and experimentation. These roles continued during and after the creation of France's largest penal colony across the territory (1852-1953). This article identifies different phases of Ilet la Mère's colonial and postcolonial histories, and argues that the island plays an integral role in the ongoing perception and administration of French Guiana as colonial outpost and underexploited natural resource. This involves frequent misconceptions that French Guiana itself is an island, and the metonymic evocation of its islands, notably Devil's Island (one of the Salvation Islands) and Cayenne, to denote the entire territory. Such perceptions, applied from outside the territory, alongside local engagement with lesser-known islands like Ilet la Mère, contribute to the creation of a 'toxic island ecology'. Toxicity, defined as more than contagion and contamination, incorporates other practices and discourses which work to draw attention away from environmental and human rights abuses taking place on the mainland. The article concludes with reflection on the island's current usage as a nature sanctuary where visitors can interact with overly tame squirrel monkeys. [ABSTRACT FROM AUTHOR]

Background: Wildlife zoos provide the opportunity for children and adults to interact with animals, However, it's unknown that the risk of contact with animals, which carried zoonotic pathogens and antimicrobial resistant bacteria. Objectives: This study aimed to investigate the prevalence and antimicrobial susceptibility of extended‐spectrum β‐lactamases Escherichia coli (ESBLs‐EC) from a wildlife zoo in China. Methods: A total of 93 wildlife faecal samples were collected from a wildlife zoo. Agar dilution method was used to determine the resistant phenotype. Whole genomes sequencing and bioinformatic analysis were employed to evaluate the molecular typing and genetic relationships of ESBLs‐EC. Results: A total of 23 CTX‐M‐positive ESBLs‐EC were isolated from swan (n = 14), squirrel monkey (n = 5), black hat hanging monkey (n = 2), gibbon monkey (n = 1) and phoenicopteridae (n = 1) respectively. All ESBLs‐EC strains were resistant to cefotaxime, tetracycline, ciprofloxacin and trimethoprim‐sulfamethoxazole, but susceptible to colistin, tigecycline, meropenem and amikacin. By screening whole genome sequences, ESBLs‐EC strains main carried blaCTX‐M‐55 (34.8%, 8/23) and blaCTX‐M‐14 (26.0%, 6/23), following by blaCTX‐M‐27 (21.7%, 5/23), blaCTX‐M‐15 (13.0%, 3/23) and blaCTX‐M‐121 (4.3%, 1/23). ESBLs‐EC strains mainly belonged to phylogroup A (60.9%, 14/23), and ST48, ST746 and ST616 (3 strains respectively, 13.0%) were major ST types. Core genome‐based single nucleotide polymorphism (SNP) analysis suggested that strains from the swan, over the phylogenetic tree, have a closer genetic relationship with strains from other animals (black hat hanging monkey, gibbon monkey, phoenicopteridae and squirrel monkey). Conclusions: CTX‐M type ESBLs‐EC can transmit between animals in wildlife zoos, which may be a risk of spread to animal keepers, veterinarians and visitors when contact with animals. Our study provides that the importance of hygiene measures to minimise the risk of transmission of ESBLs‐EC to visitors in wildlife zoos. [ABSTRACT FROM AUTHOR]

Incubation periods in humans infected with transmissible spongiform encephalopathy (TSE) agents can exceed 50 years. In humans infected with bovine spongiform encephalopathy (BSE) agents, the effects of a "species barrier," often observed when TSE infections are transmitted from one species to another, would be expected to increase incubation periods compared with transmissions of same infectious agents within the same species. As part of a long-term study investigating the susceptibility to BSE of cell cultures used to produce vaccines, we inoculated squirrel monkeys (Saimiri sp., here designated SQ) with serial dilutions of a bovine brain suspension containing the BSE agent and monitored them for as long as ten years. Previously, we showed that SQ infected with the original "classical" BSE agent (SQ-BSE) developed a neurological disease resembling that seen in humans with variant CJD (vCJD). Here, we report the final characterization of the SQ-BSE model. We observed an unexpectedly marked difference in incubation times between two animals inoculated with the same dilution and volume of the same C-BSE bovine brain extract on the same day. SQ-BSE developed, in addition to spongiform changes and astrogliosis typical of TSEs, a complex proteinopathy with severe accumulations of protease-resistant prion protein (PrPTSE), hyperphosphorylated tau (p-tau), ubiquitin, and α-synuclein, but without any amyloid plaques or β-amyloid protein (Aβ) typical of Alzheimer's disease. These results suggest that PrPTSE enhanced the accumulation of several key proteins characteristically seen in human neurodegenerative diseases. The marked variation in incubation periods in the same experimental TSE should be taken into account when modeling the epidemiology of human TSEs. [ABSTRACT FROM AUTHOR]

The TAR DNA Binding Protein (TARDBP) gene has become relevant after the discovery of its several pathogenic mutations. The lack of evolutionary history is in contrast to the amount of studies found in the literature. This study investigated the evolutionary dynamics associated with the retrotransposition of the TARDBP gene in primates. We identified novel retropseudogenes that likely originated in the ancestors of anthropoids, catarrhines, and lemuriformes, i.e. the strepsirrhine clade that inhabit Madagascar. We also found species-specific retropseudogenes in the Philippine tarsier, Bolivian squirrel monkey, capuchin monkey and vervet. The identification of a retropseudocopy of the TARDBP gene overlapping a lncRNA that is potentially expressed opens a new avenue to investigate TARDBP gene regulation, especially in the context of TARDBP associated pathologies. [ABSTRACT FROM AUTHOR]

Saccharin is a commonly used artificial sweetener that exhibits both sweetening and sweet inhibition activities. The species‐dependent response towards saccharin and the interaction between saccharin and the sweet taste receptor T1R2/T1R3 remain elusive. In this study we used mismatched chimeras of T1R2 and T1R3 and calcium mobilization functional analysis to reveal a detailed species‐dependent response towards saccharin of human, squirrel monkey, and mouse sweet taste receptors. Our findings, combined with previous results by others, suggest multiple and complex interaction modes between saccharin and the sweet taste receptor, which are helpful guidelines for effective modulation of the sweet taste by sweetener/sweet inhibitors. [ABSTRACT FROM AUTHOR]

Background: In South and Central America, Plasmodium malariae/Plasmodium brasilianum, Plasmodium vivax, Plasmodium simium, and Plasmodium falciparum has been reported in New World primates (NWP). Specifically in Costa Rica, the presence of monkeys positive to P. malariae/P brasilianum has been identified in both captivity and in the wild. The aim of the present study was to determine the presence of P. brasilianum, P. falciparum, and P. vivax, and the potential distribution of these parasites-infecting NWP from Costa Rica. Methods: The locations with PCR (Polymerase Chain Reaction) positive results and bioclimatic predictors were used to construct ecological niche models based on a modelling environment that uses the Maxent algorithm, named kuenm, capable to manage diverse settings to better estimate the potential distributions and uncertainty indices of the potential distribution. Results: PCR analysis for the Plasmodium presence was conducted in 384 samples of four primates (Howler monkey [n = 130], White-face monkey [n = 132], Squirrel monkey [n = 50], and red spider monkey [n = 72]), from across Costa Rica. Three Plasmodium species were detected in all primate species (P. falciparum, P. malariae/P. brasilianum, and P. vivax). Overall, the infection prevalence was 8.9%, but each Plasmodium species ranged 2.1–3.4%. The niche model approach showed that the Pacific and the Atlantic coastal regions of Costa Rica presented suitable climatic conditions for parasite infections. However, the central pacific coast has a more trustable prediction for malaria in primates. Conclusions: The results indicate that the regions with higher suitability for Plasmodium transmission in NWP coincide with regions where most human cases have been reported. These regions were also previously identified as areas with high suitability for vector species, suggesting that enzootic and epizootic cycles occur. [ABSTRACT FROM AUTHOR]

Humans form abstract representations about the physical properties of objects, with very young infants having ‘core knowledge’ about solidity and continuity. Whether nonhuman primates also form abstract representation of physical properties is debated. Despite studies showing that some nonhuman primates can discriminate between functional and non-functional tools, whether they achieve this by recognizing an object’s physical properties or via associative learning of perceptual cues remains contested. One method for exploring an individual’s physical cognition is the trap-tube (where subjects push a reward out of a pipe whilst avoiding a trap). The trap-tube investigates whether participants understand that rewards cannot pass through solid objects (solidity) and that unsupported objects will fall (gravity). Initial research reported that chimpanzees and capuchin monkeys solved the test using associative rules; however, modifying the task by removing the tool revealed an understanding of solidity in chimpanzees. In this series of studies, we tested 12 squirrel monkeys and 14 capuchin monkeys on a modified trap-box, where the monkeys could move the reward using their fingers rather than a tool. No individual of either species passed the task at above chance levels. In Experiment 2, the same trap blocked one of two cups: both species learned to avoid it. In Experiment 3, only capuchins generalized this solution to novel materials, performing better when cues had a functional versus a non-functional relationship to the outcome. Squirrel monkeys appeared to learn via association, while results from capuchins indicated a sensitivity to the concept of solidity.

During the Zika virus (ZIKV) outbreak and after evidence of its sexual transmission was obtained, concerns arose about the impact of the adverse effects of ZIKV infection on human fertility. In this study, we evaluated the clinical-laboratory aspects and testicular histopathological patterns of pubertal squirrel monkeys (Saimiri collinsi) infected with ZIKV, analyzing the effects at different stages of infection. The susceptibility of S. collinsi to ZIKV infection was confirmed by laboratory tests, which detected viremia (mean 1.63 × 106 RNA copies/µL) and IgM antibody induction. Reduced fecal testosterone levels, severe testicular atrophy and prolonged orchitis were observed throughout the experiment by ultrasound. At 21 dpi, testicular damage associated with ZIKV was confirmed by histopathological and immunohistochemical (IHC) analyses. Tubular retraction, the degeneration and necrosis of somatic and germ cells in the seminiferous tubules, the proliferation of interstitial cells and an inflammatory infiltrate were observed. ZIKV antigen was identified in the same cells where tissue injuries were observed. In conclusion, squirrel monkeys were found to be susceptible to the Asian variant of ZIKV, and this model enabled the identification of multifocal lesions in the seminiferous tubules of the infected group evaluated. These findings may suggest an impact of ZIKV infection on male fertility.

Animal models enable research on biological phenomena with controlled interventions not possible or ethical in patients. Among species used as experimental models, squirrel monkeys (Saimiri genus) are phylogenetically related to humans and are relatively easily managed in captivity. Quadrupedal locomotion of squirrel monkeys resembles most other quadrupedal primates in that they utilize a diagonal sequence/diagonal couplets gait when walking on small branches. However, to assume a bipedal locomotion, the human pelvis has undergone evolutionary changes. Therefore, the pelvic bone morphology is not that similar between the female squirrel monkey and woman, but pelvic floor support structures and impacts of fetal size and malpresentation are similar. Thus, this review explores the pelvic floor support structural characteristics of female squirrel monkeys, especially in relation to childbirth to demonstrate similarities to humans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268 , is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs. [ABSTRACT FROM AUTHOR]

Our research goal was to investigate the primate pet trade in the United States. While dogs and cats are the most common type of pet, there are an estimated 15,000 pet primates in the United States and the demand for exotic pets in general has been rising. Most research on pet primates occurs in habitat countries and little is known about these pets in the United States. We collected data from six exotic pet-trade websites twice a month for 12 months. We recorded the type of primate for sale, sex, age, location, and price. We used Chi-Square Goodness-of-Fit tests to compare whether the number of male and female pet primates for sale and the number of different age categories of pet primates for sale differed from equality and Spearman Correlation to examine associations between price and size and price and supply. We recorded 551 pet primates for sale between June 2019-June 2020, with 69.1% platyrrhines, 21.6% strepsirrhines, and 8.9% catarrhines. Marmosets were sold most often (36.7%, N = 202) followed by lemurs (21.6%, N = 119), capuchins (11.3%, N = 62), and squirrel monkeys (10.5%, N = 58). Almost two-thirds of the pet primates for sale were male (Chi-Square = 16.056, df = 1, P = 0. 00006) and 78.7% were under one year old (Chi-Square = 440.264, df = 2, P<0.00001). The median price was $3,800 though price was highly variable, even for the same taxa. There are several potential drivers for the primate pet trade, including media influence, fashion/status, and profitable breeding though these are not mutually exclusive. Primates do not make good pets and even when captive-bred, pet primates impact the conservation of their wild counterparts. Advertisement campaigns focusing on disease transmission and legal consequences and a federal ban on pet primate ownership are two avenues to pursue to end the ownership of pet primates in the United States. [ABSTRACT FROM AUTHOR]

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication. Measles virus is highly contagious and outbreaks occur worldwide. Here the authors show that the orally bioavailable small-molecule polymerase inhibitor ERDRP-0519 prevents measles disease in squirrel monkeys and reduces virus shedding. [ABSTRACT FROM AUTHOR]

The development of genetic manipulation of Plasmodium falciparum in the 1980s was key to study malaria biology. Genetically modified parasites have been used to study several aspects of the disease, such as red blood cell invasion, drug resistance mechanisms, gametocyte development and mosquito transmission. However, biological and genetic differences between P. falciparum and the other human malaria parasites make P. falciparum a poor model to study different species. The lack of robust systems of long-term in vitro culture of P. vivax and the other human malaria parasites lagged the genetic manipulation of these species. Here we review the efforts to generate genetically modified non- falciparum human malaria parasites, in vivo and in vitro. Using in vivo models – infection of non-human primates such as rhesus macaques and saimiri monkeys – researchers were able to generate transgenic lines of P. knowlesi, P. cynomolgi , and P. vivax. The development of long-term in vitro culture of P. knowlesi in the 2000's, using rhesus and human red blood cells, created a platform to genetically manipulate non- falciparum malaria parasites. Recently, the use of CRISPR/Cas9 technology to genome edit P. knowlesi provides another tool to non-falciparum malaria research, extending the possibilities and allowing researchers to study different aspects of the biology of these parasites and understand the differences between these species and P. falciparum. [ABSTRACT FROM AUTHOR]

Locomotion on the narrow and compliant supports of the arboreal environment is inherently precarious. Previous studies have identified a host of morphological and behavioral specializations in arboreal animals broadly thought to promote stability when on precarious substrates. Less well-studied is the role of the tail in maintaining balance. However, prior anatomical studies have found that arboreal taxa frequently have longer tails for their body size than their terrestrial counterparts, and prior laboratory studies of tail kinematics and the effects of tail reduction in focal taxa have broadly supported the hypothesis that the tail is functionally important for maintaining balance on narrow and mobile substrates. In this set of studies, we extend this work in two ways. First, we used a laboratory dataset on three-dimensional segmental kinematics and tail inertial properties in squirrel monkeys (Saimiri boliviensis) to investigate how tail angular momentum is modulated during steady-state locomotion on narrow supports. In the second study, we used a quantitative dataset on quadrupedal locomotion in wild platyrrhine monkeys to investigate how free-ranging arboreal animals adjust tail movements in response to substrate variation, focusing on kinematic measures validated in prior laboratory studies of tail mechanics (including the laboratory data presented). Our laboratory results show that S. boliviensis significantly increase average tail angular momentum magnitudes and amplitudes on narrow supports, and primarily regulate that momentum by adjusting the linear and angular velocity of the tail (rather than via changes in tail posture per se). We build on these findings in our second study by showing that wild platyrrhines responded to the precarity of narrow and mobile substrates by extending the tail and exaggerating tail displacements, providing ecological validity to the laboratory studies of tail mechanics presented here and elsewhere. In conclusion, our data support the hypothesis that the long and mobile tails of arboreal animals serve a biological role of enhancing stability when moving quadrupedally over narrow and mobile substrates. Tail angular momentum could be used to cancel out the angular momentum generated by other parts of the body during steady-state locomotion, thereby reducing whole-body angular momentum and promoting stability, and could also be used to mitigate the effects of destabilizing torques about the support should the animals encounter large, unexpected perturbations. Overall, these studies suggest that long and mobile tails should be considered among the fundamental suite of adaptations promoting safe and efficient arboreal locomotion. [ABSTRACT FROM AUTHOR]

Background Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g. methamphetamine [MA]) and/or entactogens (e.g. 3,4-methylenedioxymethaphetamine [MDMA])—presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates. Methods The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle. Results Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects. Conclusions These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans. [ABSTRACT FROM AUTHOR]

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-β, 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. [ABSTRACT FROM AUTHOR]

Play behavior is widespread in juvenile mammals and may be a mechanism for practicing skills needed in adulthood. In mammals characterized by strong adult male competition over females, juvenile males perform more social play than do females, and such play may assist in later mating competition. This study examined whether social play behavior is sexually dimorphic in a polygamous neotropical primate, the squirrel monkey (Saimiri collinsi), through a six-week field study of two groups of wild monkeys in Eastern Amazonia, Brazil. We hypothesized that males would conduct more rough-and-tumble play than females and that any sex-based play differences would be more evident in older juveniles. We video recorded juvenile play bouts and scored: age category (younger or older juvenile) and sex of players (male or female); and rough-and-tumble play behaviors (i.e., bite, grab, and wrestle). Juvenile males initiated more play bouts than did females. Most players were older juvenile males, while older juvenile females were the least represented. Older juvenile play bouts occurred mostly among males, while younger juvenile bouts consisted of a more even sex distribution. While younger juveniles did not significantly affect the number of rough-and-tumble behaviors in bouts, the number of behaviors was significantly affected by the sex of older individuals. These results indicate that social play is sexually dimorphic in juvenile S. collinsi; specifically, males play more than females and sex differences are more pronounced in older cohorts. [ABSTRACT FROM AUTHOR]