Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

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.

Receptive-field nonlinearities in primary auditory cortex: a comparative perspective.

Cortical processing of auditory information can be affected by interspecies differences as well as brain states. Here we compare multifeature spectro-temporal receptive fields (STRFs) and associated input/output functions or nonlinearities (NLs) of neurons in primary auditory cortex (AC) of four mammalian species. Single-unit recordings were performed in awake animals (female squirrel monkeys, female, and male mice) and anesthetized animals (female squirrel monkeys, rats, and cats). Neuronal responses were modeled as consisting of two STRFs and their associated NLs. The NLs for the STRF with the highest information content show a broad distribution between linear and quadratic forms. In awake animals, we find a higher percentage of quadratic-like NLs as opposed to more linear NLs in anesthetized animals. Moderate sex differences of the shape of NLs were observed between male and female unanesthetized mice. This indicates that the core AC possesses a rich variety of potential computations, particularly in awake animals, suggesting that multiple computational algorithms are at play to enable the auditory system's robust recognition of auditory events.

Signatures of adaptive evolution in platyrrhine primate genomes.

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.

Spared Premotor Areas Undergo Rapid Nonlinear Changes in Functional Organization Following a Focal Ischemic Infarct in Primary Motor Cortex of Squirrel Monkeys.

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 (-42.4%) at 3 weeks. In PMd the forelimb maps expanded significantly (+110.6%) at 2 weeks but contracted significantly (-57.4%) 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.SIGNIFICANCE STATEMENT The relationship between motor recovery and motor map reorganization after cortical injury has rarely been examined in acute/subacute periods. In nonhuman primates, premotor maps were examined at 2 and 3 weeks after injury to primary motor cortex. Although maps are known to expand late after injury, the present study demonstrates early map expansion at 2 weeks (dorsal premotor cortex) followed by contraction at 3 weeks (dorsal and ventral premotor cortex). This nonlinear map reorganization during a time of gradual behavioral recovery suggests that the relationship between map plasticity and motor recovery is much more complex than previously thought. It also suggests that rehabilitative motor training may have its most potent effects during this early dynamic phase of map reorganization.

Alternative Reinforcers Enhance the Effects of Opioid Antagonists, but Not Agonists, on Oxycodone Choice Self-Administration in Nonhuman Primates.

Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration-approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032-1.0 mg/kg), nalbuphine (0.32-10 mg/kg), buprenorphine (0.0032-0.032 mg/kg), methadone (0.32-1.0 mg/kg), or flumazenil (1-3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a µ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy µ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy µ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse-related behaviors. SIGNIFICANCE STATEMENT: Clinical treatment programs for opioid use disorder use a combination of pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective have not been fully characterized. This study examined whether the effectiveness of µ-opioid medications to decrease oxycodone self-administration is altered in the presence of an alternative reinforcer. The results suggest that alternative reinforcers enhance the effects of antagonist or low-efficacy partial agonists, suggesting they may be a more effective strategy to curtail opioid use.

Serological evidence of exposition to Toxoplasma gondii in Saimiri spp. kept in a research institution as biomodels in Rio de Janeiro.

Anti-Toxoplasma gondii antibodies were investigated in 125 Saimiri spp. kept at a research institute. A total of 12% of primates tested positive, all of which were Saimiri sciureus. These results highlight the need to minimize the possibility of this protozoan's circulation, which can lead to fulminant infection in these animals.

Functional imaging and anatomical connections in squirrel monkeys reveal parietal-frontal circuits underlying eye movements.

The posterior parietal cortex (PPC) of squirrel monkeys contains subregions where long trains of intracortical microstimulation evoke complex, behaviorally meaningful movements. Recently, we showed that such stimulation of a part of the PPC in the caudal lateral sulcus (LS) elicits eye movements in these monkeys. Here, we studied the functional and anatomical connections of this oculomotor region we call parietal eye field (PEF) with frontal eye field (FEF) and other cortical regions in 2 squirrel monkeys. We demonstrated these connections with intrinsic optical imaging and injections of anatomical tracers. Optical imaging of frontal cortex during stimulation of the PEF evoked focal functional activation within FEF. Tracing studies confirmed the functional PEF-FEF connections. Moreover, tracer injections revealed PEF connections with other PPC regions on the dorsolateral and medial brain surface, cortex in the caudal LS, and visual and auditory cortical association areas. Subcortical projections of PEF were primarily with superior colliculus, and pontine nuclei as well as nuclei of the dorsal posterior thalamus and caudate. These findings suggest that PEF in squirrel monkey is homologous to lateral intraparietal (LIP) area of macaque, supporting the notion that these brain circuits are organized similarly to mediate ethologically relevant oculomotor behaviors.

Update of the geographic range of Humboldt's squirrel monkeys (Saimiri cassiquiarensis cassiquiarensis Lesson, 1840) using a model-based approach.

Saimiri cassiquiarensis cassiquiarensis (Cebidae) is a primate subspecies with a wide distribution in the Amazonian region of Brazil, Colombia, and Venezuela. However, the boundaries of its geographic range remain poorly defined. This study presents new occurrence localities for this subspecies and updates its distribution using a compiled data set of 140 occurrence records based on literature, specimens vouchered in scientific collections, and new field data to produce model-based range maps. After cleaning our data set, we updated the subspecies' extent of occurrence, which was used in model calibration. We then modeled the subspecies' range using a maximum entropy algorithm (MaxEnt). The final model was adjusted using a fixed threshold, and we revised this polygon based on known geographic barriers and parapatric congeneric ranges. Our findings indicate that this subspecies is strongly associated with lowland areas, with consistently high daily temperatures. We propose modifications to all range boundaries and estimate that 3% of the area of occupancy (AOO, as defined by IUCN) has already been lost due to deforestation, resulting in a current range of 224,469 km2. We also found that 54% of their AOO is currently covered by protected areas (PAs). Based on these results, we consider that this subspecies is currently properly classified as Least Concern, because it occupies an extensive range, which is relatively well covered by PAs, and is currently experiencing low rates of deforestation.

Saimiri cassiquiarensis cassiquiarensis (Cebidae) é uma subespécie de primata com ampla distribuição na região amazônica do Brasil, Colômbia e Venezuela. No entanto, os limites de sua distribuição geográfica permanecem mal definidos. Este estudo apresenta novas localidades de ocorrência para essa subespécie e atualiza sua distribuição usando 140 registros de ocorrência compilados com base na literatura, espécimes depositados em coleções científicas e novos registros de campo para produzir mapas de distribuição baseados em modelos. Após a limpeza do nosso banco de dados, atualizamos a extensão de ocorrência da subespécie, que foi usada na calibração do modelo. Em seguida, modelamos a área de distribuição da subespécie usando um algoritmo de entropia máxima (MaxEnt). O modelo final foi ajustado usando um limiar fixo e revisamos esse polígono com base em barreiras geográficas conhecidas e na distribuição de congêneres parapátricas. Nosso modelo sugere que a espécie é fortemente associada a áreas planas, com temperaturas diárias consistentemente altas. Propomos modificações em todos os limites da área de distribuição e estimamos que 3% da área de ocupação (AOO, conforme definida pela IUCN) da subespécie já foi perdida devido ao desmatamento, resultando em uma área de distribuição atual de 224,469 km2. Também estimamos que 54% de sua AOO encontra­se atualmente coberta por áreas protegidas. Com base nesses resultados, consideramos que a subespécie está apropriadamente classificada como Pouco Preocupante, pois ocupa uma área extensa, que é relativamente bem coberta por áreas protegidas e atualmente apresenta baixas taxas de desmatamento.

Eat the fruit earlier: Sakis (Pithecia chrysocephala) show enhanced temporal fruit resource access compared with squirrel monkeys (Saimiri sciureus) in an urban forest fragment in Brazil.

Fruit availability experienced by different primate species is likely to vary due to species-specific fruit use, even within the same habitat and timeframe. Pitheciines, primates of the subfamily Pitheciinae, particularly favor the seeds of unripe fruits. Researchers consider this dietary characteristic an adaptation to increase access to fruit resources. However, the relative advantages of pitheciines over sympatric non-pitheciine non-seed-eating primates regarding species-specific fruit availability is not well studied. In a 26-ha forest within the city of Manaus, Amazonian Brazil, we assessed the wild-food feeding behavior of free-ranging groups of golden-faced sakis (Pithecia chrysocephala) and sympatric common squirrel monkeys (Saimiri sciureus). We hypothesized that sakis would have greater and more consistent access to wild fruit due to (1) a wider variety of fruit species in their diet, and (2) longer consumption periods per fruit species. We recorded the plant species, part (pulp or seed), and developmental stage (ripe or unripe) of wild fruit consumed by both species. We also conducted monthly fruit censuses of 1000 trees and vines to estimate overall wild fruit abundance. As an indicator of fruit availability, we calculated the proportion of available fruiting trees and vines for each primate species separately based on their observed diet. Throughout the year, the proportion of available trees and vines was significantly higher and more temporally stable for sakis than for squirrel monkeys. This was because sakis used shared fruit species longer than squirrel monkeys by consuming both ripe and unripe fruit. Although sakis had a broader fruit repertoire than squirrel monkeys, it did not contribute to the higher fruit availability. Thus, the fruit feeding system of sakis identifies aspects of a niche that is less restricted in the timing of fruit consumption, which led to a relative advantage in fruit availability.

DETECTION OF SARS-COV-2 IN A SQUIRREL MONKEY (SAIMIRI SCIUREUS): A ONE HEALTH INVESTIGATION AND RESPONSE.

Through collaborative efforts, One Health partners have responded to outbreaks of COVID-19 among animals, including those in human care at zoos. Zoos have been faced with numerous challenges, including the susceptibility of many mammalian species, and therefore the need to heighten biosecurity measures rapidly. Robust One Health collaborations already exist in Arizona to address endemic and emerging zoonoses, but these have rarely included zoos. The pandemic shed light on this, and Arizona subsequently expanded its SARS-CoV-2 surveillance efforts to include zoo animals. Testing and epidemiologic support was provided to expedite the detection of and response to zoonotic SARS-CoV-2 infection in zoo animals, as well as to understand possible transmission events. Resulting from this program, SARS-CoV-2 was detected from a rectal swab collected from an 8-yr-old squirrel monkey (Saimiri sciureus) from a zoo in Southern Arizona. The animal had rapidly become ill with nonrespiratory symptoms and died in July 2022. Genomic sequencing from the swab revealed mutations consistent with the Omicron (BA.2) lineage. An epidemiologic investigation identified an animal caretaker in close proximity to the affected squirrel monkey who tested positive for COVID-19 the same day the squirrel monkey died. Critical One Health partners provided support to the zoo through engagement of local, state, and federal agencies. Necropsy and pathologic evaluation showed significant necrotizing colitis; the overall clinical and histopathological findings did not implicate SARS-CoV-2 infection alone as a causal or contributing factor in the squirrel monkey's illness and death. This report documents the first identification of SARS-CoV-2 in a squirrel monkey and highlights a successful and timely One Health investigation conducted through multisectoral collaboration.

Differential Recovery of Submodality Touch Neurons and Interareal Communication in Sensory Input-Deprived Area 3b and S2 Cortices.

Cortical reactivation and regain of interareal functional connections have been linked to the recovery of hand grasping behavior after loss of sensory inputs in primates. We investigated contributions of neurons in two hierarchically organized somatosensory areas, 3b and S2, by characterizing local field potential (LFP) and multiunit spiking activity in five states (rest, stimulus-on, sustained, stimulus-off, and induced) and interareal communication after grasping behavior of dorsal column lesioned male squirrel monkeys had mostly recovered. Compared with normal cortex, fMRI, LFP, and spiking response magnitudes to step indentations were significantly weaker. The sustained component of the spiking recovered much better than the stimulus-off response. Correlation between overall spiking and γ LFP remained strong within each recovered areas 3b and S2. The interareal correlations of γ LFP were severely disrupted, except in the resting and stimulus-on periods. Interareal correlation of spiking was disrupted in the stimulus-off period only. In summary, submodality of low threshold mechanoreceptive neurons recovered differentially in input-deprived area 3b and S2 when impaired global hand grasping behavior returned. Slow-adapting-like neurons recovered, whereas rapid-adapting-like neurons did not. Interareal communications were also severely compromised. We propose that slow-adapting-like neurons and afferents in recovered area 3b and S2 mediate recovery of impaired grasping behavior after dorsal column tract lesion.SIGNIFICANCE STATEMENT Sensory feedback is essential for execution of hand grasping behavior in primates. Reactivations of somatosensory cortices have been attributed to recovery of such behavior after loss of sensory inputs via largely unknown mechanisms. In input-deprived area 3b and S2 cortex, after hand grasping behavior mostly recovered, we found slow-adapting-like neurons were greatly recovered, whereas rapid-adapting-like neurons did not. Communications between area 3b and S2 neurons were severely compromised. We suggest that recovery of slow-adapting-like neurons in input-deprived area 3b and S2 may mediate the recovery of hand grasping behavior.

Single-cell transcription analysis of Plasmodium vivax blood-stage parasites identifies stage- and species-specific profiles of expression.

Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215 P. vivax parasites from bloodstream infections of Aotus and Saimiri monkeys. Our results show that transcription of most P. vivax genes occurs during short periods of the intraerythrocytic cycle and that this pattern of gene expression is conserved in other Plasmodium species. However, we also identify a strikingly high proportion of species-specific transcripts in late schizonts, possibly associated with the specificity of erythrocyte invasion. Our findings provide new and robust markers of blood-stage parasites, including some that are specific to the elusive P. vivax male gametocytes, and will be useful for analyzing gene expression data from laboratory and field samples.

In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.

Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Genetic manipulations (GM) of pigs offer the possibility of reducing primate humoral and cellular rejection of pig skin xenografts and thus extending graft survival. We compared the survival of skin grafts from pigs with 9-GM with that of autografts and allografts in squirrel monkeys. Monitoring for rejection was by (1) macroscopic examination, (2) histopathological examination of skin biopsies, and (3) measurement of anti-monkey and anti-pig IgM and IgG antibodies. Autografts (n = 5) survived throughout the 28 days of follow-up without histopathological features of rejection. Median survival of allografts (n = 6) was 14 days and of pig xenografts (n = 12) 21 days. Allotransplantation was associated with an increase in anti-monkey IgM, but the anticipated subsequent rise in IgG had not yet occurred at the time of euthanasia. Pig grafts were associated with increases in anti-pig IgM and IgG. In all cases, histopathologic features of rejection were similar. 9-GM pig skin xenografts survive at least as long as monkey skin allografts (and trended to survive longer), suggesting that they are a realistic clinical option for the temporary treatment of burns. Although monkeys with pig skin grafts developed anti-pig IgM and IgG antibodies, these did not cross-react with monkey antigens, indicating that a primary 9-GM pig skin graft would not be detrimental to a subsequent monkey skin allograft.

Filarial hyperinfection in two neotropical primates from eastern Amazon peri-urban areas.

We report two cases of disseminated hyperinfection by filariae in free-living primates Saimiri sciureus and Saguinus niger from eastern Amazon. Histopathological examination showed the presence of Dipetalonema gracile microfilariae in blood, liver, lungs, spleen, small intestine, kidney, brain, liver, and adults in peritoneal thoracic cavity.

Seasonal variations in gonadosomatic index and seminal quality of squirrel monkeys (Saimiri collinsi).

BACKGROUND: We hypothesized that seasonal variations in testicular biometry in Saimiri collinsi are influenced by body mass and that testicular enlargement is related to improved seminal quality. Therefore, the gonadosomatic index (GSI) can be a tool to determine reproductive seasons and the predictors of seminal quality. METHODS: Body mass, testicular biometry, and semen samples were obtained from eight adult males monthly and evaluated. RESULTS: In the non-fattening/non-reproductive season, the body mass and GSI decreased and increased, respectively, in the fattening. A positive correlation was only observed between the GSI and seminal volume. During fattening, high seminal volume and normal morphology were observed, but sperm concentrations were low. CONCLUSION: The GSI cannot be used as a predictor of seminal quality, but selective pressure to improve seminal quality may increase the chances of fertilization at fattening. The GSI provides new information on seasonality and can be used to identify reproductive seasons in squirrel monkeys.

Disseminated histiocytic sarcoma in a squirrel monkey (Saimiri sciureus).

A 14-years-old squirrel monkey was euthanized due to weakness. Histopathological examination revealed multifocal growth of oval cells with severe atypia in the liver, spleen, and bone marrow. The neoplastic cells were positive for histiocytic markers (Iba1, HLA-DR, CD204). This is the fourth case of histiocytic sarcoma in non-human primates.

Morphometry of cryopreserved organs from the gastrointestinal system of squirrel monkeys (Saimiri sciureus, Linnaeus, 1758) for improvement of management.

BACKGROUND: Nonhuman primates (NHPs) are fundamental for countless types of research and their phylogenetic similarities with humans make them valuable biomodels. Saimiri (squirrel monkeys) is the New World simian genus that is most widely used in research; however, little is known about the morphology of the gastrointestinal tract (GIT) of these animals. METHODS: The morphological and topographical aspects of GIT organs from 14 previously frozen carcasses of captive squirrel monkeys (Saimiri sciureus) were described as a means for refining clinical and laboratory diagnoses, with the aim of providing a basis for clinical assessments and animal management. The carcasses were gradually thawed, macroscopically evaluated for their appearance, measured, weighed, photographed, and necropsied. The characteristics of all the GIT organs (main and accessories) were evaluated, with measurement of the dimensions and description of the shape, consistency, and color of each one. RESULTS: The stomach of squirrel monkeys is simple and of non-compartmentalized type and the cecum does not have numerous folds, compared with other species. These characteristics are compatible with omnivorous simian species with no adaptive digestive specialization for the food fermentation process. Significant correlations were found between the weights of the carcass and GIT (p < .05); carcass and tongue (0.83; p < .01); and liver and right salivary gland (0.83; p < .01). It was also observed that the animals showed good body score conformation and GIT organs in good condition, which indicated that their nutritional management had been adequate. Regarding the correlations found among the organs: (i) squirrel monkeys with heavier carcasses had better-developed GIT with greater food storage capacity; (ii) the bigger the animal was, the greater its overall muscle development was, including that of the tongue, which would enable intensification of its feeding activity; and (iii) the measurements of the esophagus, small and large intestines, pancreas, and salivary glands were not sex-dependent in Saimiri sciureus. CONCLUSIONS: Previously cryopreserved carcasses of squirrel monkeys can be used for gastrointestinal system studies, with the potential to make clinical, zootechnical, management, and scientific contributions.

SELECTED OPHTHALMIC TESTS AND OCULAR DIMENSIONS IN RELATION TO ACTIVITY PATTERN IN THREE NEOTROPICAL NONHUMAN PRIMATES: BLACK-TUFTED MARMOSET (CALLITHRIX PENICILLATA), GUIANAN SQUIRREL MONKEY (SAIMIRI SCIUREUS), AND AZARA'S NIGHT MONKEY (AOTUS AZARAE INFULATUS).

The goals of this study were to compare ocular morphology, determine the reference intervals of selected ophthalmic tests, ocular measurements, intraocular pressure, and tear production, and to establish possible relationships in the visual ecology of three different Neotropical nonhuman primates (NHP). Nineteen black-tufted marmosets (Callithrix penicillate), 24 Guianan squirrel monkeys (Saimiri sciureus), and 24 night monkeys (Aotus azarae infulatus) were included in the study. Schirmer tear test, ocular dimensions, ocular ultrasonography, intraocular pressure, central corneal thickness, and corneal touch threshold were determined. The ratio of the average corneal diameters and axial diameters (CD/AGL) were established. No significant difference was noted between males and females, nor left and right eyes, for all three species for all measurements (P > 0.05). CD/AGL ratio was significantly higher (P < 0.0001) in night monkeys (a nocturnal species) as compared to black-tufted marmoset and Guianan squirrel monkeys (two diurnal species). The reference intervals will aid veterinary ophthalmologists to more accurately diagnose pathological changes in the eyes of these species. In addition, ocular dimension comparison will allow other NHP species to be evaluated and examined in relationship to behavioral traits (nocturnal versus diurnal).

Presence and potential distribution of malaria-infected New World primates of Costa Rica.

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.

Innate immunity stimulation via CpG oligodeoxynucleotides ameliorates Alzheimer's disease pathology in aged squirrel monkeys.

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.