Recapitulation of HIV-1 Neutralization Breadth in Plasma by the Combination of Two Broadly Neutralizing Antibodies from Different Lineages in the Same SHIV-Infected Rhesus Macaque.

Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rhesus macaques infected with SHIV1157ipd3N4 for 5 years. One lineage of neutralizing antibodies (JT15 and JT16) targeted the V2-apex in the Env trimers, similar to the J038 lineage bnAbs identified in our previous study. The other lineage neutralizing antibody (JT18) targeted the V3 crown region in the Env, which strongly competed with human 447-52D. Each lineage antibody neutralized a different set of viruses. Interestingly, when the two neutralizing antibodies from different lineages isolated from the same macaque were combined, the mixture had a neutralization breath very similar to that from the cognate sera. Our study demonstrated that a minimum of two different neutralizing antibodies can fully recapitulate the serum neutralization breadth. This observation can have important implications in AIDS vaccine design.

Factorized visual representations in the primate visual system and deep neural networks.

Object classification has been proposed as a principal objective of the primate ventral visual stream and has been used as an optimization target for deep neural network models (DNNs) of the visual system. However, visual brain areas represent many different types of information, and optimizing for classification of object identity alone does not constrain how other information may be encoded in visual representations. Information about different scene parameters may be discarded altogether ('invariance'), represented in non-interfering subspaces of population activity ('factorization') or encoded in an entangled fashion. In this work, we provide evidence that factorization is a normative principle of biological visual representations. In the monkey ventral visual hierarchy, we found that factorization of object pose and background information from object identity increased in higher-level regions and strongly contributed to improving object identity decoding performance. We then conducted a large-scale analysis of factorization of individual scene parameters - lighting, background, camera viewpoint, and object pose - in a diverse library of DNN models of the visual system. Models which best matched neural, fMRI, and behavioral data from both monkeys and humans across 12 datasets tended to be those which factorized scene parameters most strongly. Notably, invariance to these parameters was not as consistently associated with matches to neural and behavioral data, suggesting that maintaining non-class information in factorized activity subspaces is often preferred to dropping it altogether. Thus, we propose that factorization of visual scene information is a widely used strategy in brains and DNN models thereof.

When looking at a picture, we can quickly identify a recognizable object, such as an apple, applying a single word label to it. Although extensive neuroscience research has focused on how human and monkey brains achieve this recognition, our understanding of how the brain and brain-like computer models interpret other complex aspects of a visual scene ­ such as object position and environmental context ­ remains incomplete. In particular, it was not clear to what extent object recognition comes at the expense of other important scene details. For example, various aspects of the scene might be processed simultaneously. On the other hand, general object recognition may interfere with processing of such details. To investigate this, Lindsey and Issa analyzed 12 monkey and human brain datasets, as well as numerous computer models, to explore how different aspects of a scene are encoded in neurons and how these aspects are represented by computational models. The analysis revealed that preventing effective separation and retention of information about object pose and environmental context worsened object identification in monkey cortex neurons. In addition, the computer models that were the most brain-like could independently preserve the other scene details without interfering with object identification. The findings suggest that human and monkey high level ventral visual processing systems are capable of representing the environment in a more complex way than previously appreciated. In the future, studying more brain activity data could help to identify how rich the encoded information is and how it might support other functions like spatial navigation. This knowledge could help to build computational models that process the information in the same way, potentially improving their understanding of real-world scenes.

Unraveling the enigmatic role of the subthalamic nucleus.

Subpopulations of neurons in the subthalamic nucleus have distinct activity patterns that relate to the three hypotheses of the Drift Diffusion Model.

Fatal coinfection of blastocystosis and intestinal trichomoniasis in a rhesus macaque (Macaca mulatta).

A 3-year-old male rhesus macaque was presented at Referral Veterinary Polyclinic-Teaching Veterinary Clinical Complex, with a chief complaint of chronic diarrhoea and swelling of dependent body parts. The patient's history indicates that the monkey had been experiencing diarrhoea for the past month, with 2-3 episodes of vomiting in the last 2 days. Additionally, oedema has developed within the last 2 weeks. The clinical examination findings revealed dullness and depression, the mucus membrane appeared pale, with a temperature-102.1 °F, a respiration rate-28/min, and a heart rate-92/min. The capillary refill time was 4 s. During the physical examination, the animal exhibited oedema on the dependent part of the body and faecal staining around the perineum along with loose yellow stool. Direct saline and iodine mount faecal smear examination revealed the presence of many motile pear-shaped flagellated protozoa and round vacuolated Blastocystis organisms. Giemsa-stained faecal smear cytology confirmed the presence of Pentatrichomonas sp. and Blastocystis sp. along with many microbes. The faecal culture was negative for all pathogenic microbes. The case was diagnosed as co-infection Blastocystosis and intestinal trichomoniasis. The treatment was initiated with a combination of sulfamethoxazole + trimethoprim @ 35 mg/kg body weight and metronidazole @25 mg/kg administered orally once daily for 7 days. Supportive therapy includes hematinic injection (iron sorbitol, folic acid and vitamin B12) @ 1 ml total dose, administered intramuscularly on alternate days for four occasions as well as intravenous infusion of crystalline amino acid @ 5 ml total dose on alternate days for four occasions. To manage vomition, injection ondansetron was administered@0.5 mg/kg intramuscularly, twice daily for 3 days and H2 blockers, including injection ranitidine@2 mg/kg intramuscularly twice daily for 3 days. Electrolyte and probiotic supplementation were administered orally. After 7 days of therapy, the oedema had significantly improved and episodes of vomition were stopped but there was no significant improvement in the episode of diarrhoea and consistency of faeces. Unfortunately, on the 10th day of therapy, the animal suddenly collapsed. Understanding the virulence pattern of opportunistic protozoa in primates is crucial, and identifying suitable therapeutic candidates to prevent fatal outcomes is the need of the hour, especially considering protozoal infections as an important differential diagnosis in gastrointestinal tract-related ailments. Our study successfully demonstrated the co-occurrence of blastocystosis and intestinal trichomoniasis, both uncommon infections with potential zoonotic implications.

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.

Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.

Regional and cellular organization of the autism-associated protein UBE3A/E6AP and its antisense transcript in the brain of the developing rhesus monkey.

Angelman syndrome (AS) is a neurogenetic disorder caused by mutations or deletions in the maternally-inherited UBE3A allele, leading to a loss of UBE3A protein expression in neurons. The paternally-inherited UBE3A allele is epigenetically silenced in neurons during development by a noncoding transcript (UBE3A-ATS). The absence of neuronal UBE3A results in severe neurological symptoms, including speech and language impairments, intellectual disability, and seizures. While no cure exists, therapies aiming to restore UBE3A function-either by gene addition or by targeting UBE3A-ATS-are under development. Progress in developing these treatments relies heavily on inferences drawn from mouse studies about the function of UBE3A in the human brain. To aid translational efforts and to gain an understanding of UBE3A and UBE3A-ATS biology with greater relevance to human neurodevelopmental contexts, we investigated UBE3A and UBE3A-ATS expression in the developing brain of the rhesus macaque, a species that exhibits complex social behaviors, resembling aspects of human behavior to a greater degree than mice. Combining immunohistochemistry and in situ hybridization, we mapped UBE3A and UBE3A-ATS regional and cellular expression in normal prenatal, neonatal, and adolescent rhesus macaque brains. We show that key hallmarks of UBE3A biology, well-known in rodents, are also present in macaques, and suggest paternal UBE3A silencing in neurons-but not glial cells-in the macaque brain, with onset between gestational day 48 and 100. These findings support proposals that early-life, perhaps even prenatal, intervention is optimal for overcoming the maternal allele loss of UBE3A linked to AS.

Effects of repeated alcohol abstinence on within-subject prefrontal cortical gene expression in rhesus macaques.

Male rhesus monkeys (n = 24) had a biopsy of prefrontal cortical area 46 prior to chronic ethanol self-administration (n = 17) or caloric control (n = 7). Fourteen months of daily self-administration (water vs. 4% alcohol, 22 h access/day termed "open-access") was followed by two cycles of prolonged abstinence (5 weeks) each followed by 3 months of open-access alcohol and a final abstinence followed by necropsy. At necropsy, a biopsy of Area 46, contralateral to the original biopsy, was obtained. Gene expression data (RNA-Seq) were collected comparing biopsy/necropsy samples. Monkeys were categorized by drinking status during the final post-abstinent drinking phase as light (LD), binge (BD), heavy (HD) and very heavy (VHD drinkers). Comparing pre-ethanol to post-abstinent biopsies, four animals that converted from HD to VHD status had significant ontology enrichments in downregulated genes (necropsy minus biopsy n = 286) that included immune response (FDR < 9 × 10-7) and plasma membrane changes (FDR < 1 × 10-7). Genes in the immune response category included IL16 and 18, CCR1, B2M, TLR3, 6 and 7, SP2 and CX3CR1. Upregulated genes (N = 388) were particularly enriched in genes associated with the negative regulation of MAP kinase activity (FDR < 3 × 10-5), including DUSP 1, 4, 5, 6 and 18, SPRY 2, 3, and 4, SPRED2, BMP4 and RGS2. Overall, these data illustrate the power of the NHP model and the within-subject design of genomic changes due to alcohol and suggest new targets for treating severe escalated drinking following repeated alcohol abstinence attempts.

The Maintenance of Deleterious Variation in Wild Chinese Rhesus Macaques.

Understanding how deleterious variation is shaped and maintained in natural populations is important in conservation and evolutionary biology, as decreased fitness caused by these deleterious mutations can potentially lead to an increase in extinction risk. It is known that demographic processes can influence these patterns. For example, population bottlenecks and inbreeding increase the probability of inheriting identical-by-descent haplotypes from a recent common ancestor, creating long tracts of homozygous genotypes called runs of homozygosity (ROH), which have been associated with an accumulation of mildly deleterious homozygotes. Counter intuitively, positive selection can also maintain deleterious variants in a population through genetic hitchhiking. Here we analyze the whole genomes of 79 wild Chinese rhesus macaques across five subspecies and characterize patterns of deleterious variation with respect to ROH and signals of recent positive selection. We show that the fraction of homozygotes occurring in long ROH is significantly higher for deleterious homozygotes than tolerated ones, whereas this trend is not observed for short and medium ROH. This confirms that inbreeding, by generating these long tracts of homozygosity, is the main driver of the high burden of homozygous deleterious alleles in wild macaque populations. Furthermore, we show evidence that homozygous LOF variants are being purged. Next, we identify 7 deleterious variants at high frequency in regions putatively under selection near genes involved with olfaction and other processes. Our results shed light on how evolutionary processes can shape the distribution of deleterious variation in wild non-human primates.

Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection.

Nontuberculous mycobacteria (NTM) are environmentally ubiquitous organisms that predominately cause NTM pulmonary disease (NTMPD) in individuals over the age of 65. The incidence of NTMPD has increased in the U.S., exceeding that of Mycobacterium tuberculosis. However, the mechanisms leading to higher susceptibility and severity of NTMPD with aging are poorly defined in part due to the lack of animal models that accurately recapitulate human disease. Here, we compared bacterial load, microbial communities, and host responses longitudinally between three young (two female and one male) and two aged (two female) rhesus macaques inoculated with Mycobacterium avium subsp. hominissuis (MAH) in the right caudal lobe. Unilateral infection resulted in a low bacterial load in both young and aged animals confined to the infected side. Although a robust inflammatory response was only observed in the inoculated lung, immune cell infiltration and antigen-specific T cells were detected in both lungs. Computed tomography, gross pathology, and histopathology revealed increased disease severity and persistence of bacterial DNA in aged animals. Additional analyses showed the translocation of gut and oral-pharyngeal bacterial DNA into the lower respiratory microbiome. Finally, single-cell RNA sequencing revealed a heightened inflammatory response to MAH infection by alveolar macrophages in aged animals. These data are consistent with the model that increased disease severity in the aged is mediated by a dysregulated macrophage response that may be sustained through persistent antigen presence. IMPORTANCE: Nontuberculous mycobacteria (NTM) are emerging as pathogens of high consequence, as cases of NTM pulmonary disease (NTMPD) have exceeded those of Mycobacterium tuberculosis. NTMPD can be debilitating, particularly in patients over 65 years of age, as it causes chronic cough and fatigue requiring prolonged treatments with antibiotics. The underlying mechanisms of this increased disease severity with age are poorly understood, hampering the development of therapeutics and vaccines. Here, we use a rhesus macaque model to investigate the impact of age on host-NTM interactions. This work shows that aging is associated with increased disease severity and bacterial persistence in aged rhesus macaques, thus providing a preclinical model to develop and test novel therapeutics and interventions.

Comparison of electrical microstimulation artifact removal methods for high-channel-count prostheses.

BACKGROUND: Neuroprostheses are used to electrically stimulate the brain, modulate neural activity and restore sensory and motor function following injury or disease, such as blindness, paralysis, and other movement and psychiatric disorders. Recordings are often made simultaneously with stimulation, allowing the monitoring of neural signals and closed-loop control of devices. However, stimulation-evoked artifacts may obscure neural activity, particularly when stimulation and recording sites are nearby. Several methods have been developed to remove stimulation artifacts, but it remains challenging to validate and compare these methods because the 'ground-truth' of the neuronal signals may be contaminated by artifacts. NEW METHOD: Here, we delivered stimulation to the visual cortex via a high-channel-count prosthesis while recording neuronal activity and stimulation artifacts. We quantified the waveforms and temporal properties of stimulation artifacts from the cortical visual prosthesis (CVP) and used them to build a dataset, in which we simulated the neuronal activity and the stimulation artifacts. We illustrate how to use the simulated data to evaluate the performance of six software-based artifact removal methods (Template subtraction, Linear interpolation, Polynomial fitting, Exponential fitting, SALPA and ERAASR) in a CVP application scenario. RESULTS: We here focused on stimulation artifacts caused by electrical stimulation through a high-channel-count cortical prosthesis device. We find that the Polynomial fitting and Exponential fitting methods outperform the other methods in recovering spikes and multi-unit activity. Linear interpolation and Template subtraction recovered the local-field potentials. CONCLUSION: Polynomial fitting and Exponential fitting provided a good trade-off between the quality of the recovery of spikes and multi-unit activity (MUA) and the computational complexity for a cortical prosthesis.

Generation of Rhesus Macaque Embryos with Expanded CAG Trinucleotide Repeats in the Huntingtin Gene.

Huntington's disease (HD) arises from expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. The resultant misfolded HTT protein accumulates within neuronal cells, negatively impacting their function and survival. Ultimately, HTT accumulation results in cell death, causing the development of HD. A nonhuman primate (NHP) HD model would provide important insight into disease development and the generation of novel therapies due to their genetic and physiological similarity to humans. For this purpose, we tested CRISPR/Cas9 and a single-stranded DNA (ssDNA) containing expanded CAG repeats in introducing an expanded CAG repeat into the HTT gene in rhesus macaque embryos. Analyses were conducted on arrested embryos and trophectoderm (TE) cells biopsied from blastocysts to assess the insertion of the ssDNA into the HTT gene. Genotyping results demonstrated that 15% of the embryos carried an expanded CAG repeat. The integration of an expanded CAG repeat region was successfully identified in five blastocysts, which were cryopreserved for NHP HD animal production. Some off-target events were observed in biopsies from the cryopreserved blastocysts. NHP embryos were successfully produced, which will help to establish an NHP HD model and, ultimately, may serve as a vital tool for better understanding HD's pathology and developing novel treatments.

The Maintenance of Deleterious Variation in Wild Chinese Rhesus Macaques.

Understanding how deleterious variation is shaped and maintained in natural populations is important in conservation and evolutionary biology, as decreased fitness caused by these deleterious mutations can potentially lead to an increase in extinction risk. It is known that demographic processes can influence these patterns. For example, population bottlenecks and inbreeding increase the probability of inheriting identical-by-descent haplotypes from a recent common ancestor, creating long tracts of homozygous genotypes called runs of homozygosity (ROH), which have been associated with an accumulation of mildly deleterious homozygotes. Counterintuitively, positive selection can also maintain deleterious variants in a population through genetic hitchhiking. Here, we analyze the whole genomes of 79 wild Chinese rhesus macaques across five subspecies and characterize patterns of deleterious variation with respect to ROH and signals of recent positive selection. We show that the fraction of homozygotes occurring in long ROH is significantly higher for deleterious homozygotes than tolerated ones, whereas this trend is not observed for short and medium ROH. This confirms that inbreeding, by generating these long tracts of homozygosity, is the main driver of the high burden of homozygous deleterious alleles in wild macaque populations. Furthermore, we show evidence that homozygous LOF variants are being purged. Next, we identify seven deleterious variants at high frequency in regions putatively under selection near genes involved with olfaction and other processes. Our results shed light on how evolutionary processes can shape the distribution of deleterious variation in wild nonhuman primates.

Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making.

The discovery of rapid-acting antidepressant, ketamine has opened a pathway to a new generation of treatments for depression, and inspired neuroscientific investigation based on a new perspective that non-adaptive changes in the intrinsic excitatory and inhibitory circuitry might underlie the pathophysiology of depression. Nevertheless, it still remains largely unknown how the hypothesized molecular and synaptic levels of changes in the circuitry might mediate behavioral and neuropsychological changes underlying depression, and how ketamine might restore adaptive behavior. Here, we used computational models to analyze behavioral changes induced by therapeutic doses of ketamine, while rhesus macaques were iteratively making decisions based on gains and losses of tokens. When administered intramuscularly or intranasally, ketamine reduced the aversiveness of undesirable outcomes such as losses of tokens without significantly affecting the evaluation of gains, behavioral perseveration, motivation, and other cognitive aspects of learning such as temporal credit assignment and time scales of choice and outcome memory. Ketamine's potentially antidepressant effect was separable from other side effects such as fixation errors, which unlike outcome evaluation, was readily countered with strong motivation to avoid errors. We discuss how the acute effect of ketamine to reduce the initial impact of negative events could potentially mediate longer-term antidepressant effects through mitigating the cumulative effect of those events produced by slowly decaying memory, and how the disruption-resistant affective memory might pose challenges in treating depression. Our study also invites future investigations on ketamine's antidepressant action over diverse mood states and with affective events exerting their impacts at diverse time scales.

Maintenance of caecal homeostasis by diverse adaptive immune cells in the rhesus macaque.

Objectives: The caecum bridges the small and large intestine and plays a front-line role in discriminating gastrointestinal antigens. Although dysregulated in acute and chronic conditions, the tissue is often overlooked immunologically. Methods: To address this issue, we applied single-cell transcriptomic-V(D)J sequencing to FACS-isolated CD45+ caecal patch/lamina propria leukocytes from a healthy (5-year-old) female rhesus macaque ex vivo and coupled these data to VDJ deep sequencing reads from haematopoietic tissues. Results: We found caecal NK cells and ILC3s to co-exist with a spectrum of effector T cells partially derived from SOX4 + recent thymic emigrants. Tolerogenic Vγ8Vδ1-T cells, plastic CD4+ T helper cells and GZMK + EOMES + and TMIGD2 + tissue-resident memory CD8+ T cells were present and differed metabolically. An IL13 + GATA3 + Th2 subset expressing eicosanoid pathway enzymes was accompanied by IL1RL1 + GATA3 + regulatory T cells and a minor proportion of IgE+ plasma cells (PCs), illustrating tightly regulated type 2 immunity devoid of ILC2s. In terms of B lymphocyte lineages, caecal patch antigen-presenting memory B cells sat alongside germinal centre cells undergoing somatic hypermutation and differentiation into IGF1 + PCs. Prototypic gene expression signatures decreased across PC clusters, and notably, expanded IgA clonotypes could be traced in VDJ deep sequencing reads from additional compartments, including the bone marrow, supporting that these cells contribute a steady stream of systemic antibodies. Conclusions: The data advance our understanding of caecal immunological function, revealing processes involved in barrier maintenance and molecular networks relevant to disease.

The phylogenetic relationship and demographic history of rhesus macaques (Macaca mulatta) in subtropical and temperate regions, China.

Pleistocene climatic oscillations exerted significant influences on the genetic structure and demography of rhesus macaque (Macaca mulatta) in eastern China. However, the evolutionary history of rhesus macaques in subtropical and temperate China remained unclear and/or controversial. Herein, we analyzed the autosomes, mitochondrial genomes, and Y-chromosomes from 84 individuals of Chinese rhesus macaque. The results revealed that (1) all individuals were clustered into pan-west and pan-east genetic groups, which exhibited Shaanxi Province as the northernmost region of western dispersal route of rhesus macaques in China; (2) in subtropical and temperate China, rhesus macaques were divided into four lineages (TH, DB, HS, and QL), and their divergence times corresponded to the Penultimate Glaciation (300-130 kya) and Last Glaciation (70-10 kya), respectively; (3) the individuals from Mt. Taihangshan (TH) are closely related to individuals from Mt. Dabashan (DB) in the autosomal tree, rather than individuals from Mt. Huangshan (HS) as indicated by the mitogenome tree, which supports the hypothesis that the ancestral rhesus macaques radiated into Mt. Taihangshan from Mt. Huangshan via Mt. Dabashan; and (4) the demographic scenario of the four lineages showed the ancestral rhesus macaques bottleneck and expansion corresponding to the suitable habitat reduction and expansion, which confirmed they had experienced northward recolonization and southward retreat events from Mt. Huangshan area via Northern China Plain to Northernmost China along with Pleistocene glacial cycles. This study provides a new insight into understanding how Pleistocene glaciation has influenced faunal diversity in subtropical and temperate China, especially for those exhibiting differential patterns of sex dispersal.

Long-term calorie restriction reduces oxidative DNA damage to oligodendroglia and promotes homeostatic microglia in the aging monkey brain.

Calorie restriction (CR) is a robust intervention that can slow biological aging and extend lifespan. In the brain, terminally differentiated neurons and glia accumulate oxidative damage with age, reducing their optimal function. We investigated if CR could reduce oxidative DNA damage to white matter oligodendrocytes and microglia. This study utilized post-mortem brain tissue from rhesus monkeys that died after decades on a 30 % reduced calorie diet. We found that CR subjects had significantly fewer cells with oxidative damage within the corpus callosum and the cingulum bundle. Oligodendrocytes specifically showed the greatest response to CR with a robust reduction in DNA damage. Additionally, we observed alterations in microglia morphology with CR subjects having a higher proportion of ramified, homeostatic microglia and fewer pro-inflammatory, hypertrophic microglia relative to controls. Furthermore, we determined that the observed attenuation in damaged DNA occurs primarily within mitochondria. Overall, these data suggest that long-term CR can reduce oxidative DNA damage and offer a neuroprotective effect in a cell-type-specific manner in the aging monkey brain.

Inferring control objectives in a virtual balancing task in humans and monkeys.

Natural behaviors have redundancy, which implies that humans and animals can achieve their goals with different strategies. Given only observations of behavior, is it possible to infer the control objective that the subject is employing? This challenge is particularly acute in animal behavior because we cannot ask or instruct the subject to use a particular strategy. This study presents a three-pronged approach to infer an animal's control objective from behavior. First, both humans and monkeys performed a virtual balancing task for which different control strategies could be utilized. Under matched experimental conditions, corresponding behaviors were observed in humans and monkeys. Second, a generative model was developed that represented two main control objectives to achieve the task goal. Model simulations were used to identify aspects of behavior that could distinguish which control objective was being used. Third, these behavioral signatures allowed us to infer the control objective used by human subjects who had been instructed to use one control objective or the other. Based on this validation, we could then infer objectives from animal subjects. Being able to positively identify a subject's control objective from observed behavior can provide a powerful tool to neurophysiologists as they seek the neural mechanisms of sensorimotor coordination.

Epidemiological investigation of Entamoeba in wild rhesus macaques in China: A novel ribosomal lineage and genetic differentiation of Entamoeba nuttalli.

Wild rhesus macaques are a potential source of zoonotic parasites for humans, and Entamoeba spp. are common intestinal parasites. To investigate the prevalence of Entamoeba in wild rhesus macaques in China and explore the genetic differentiation of the potentially pathogenic species Entamoeba nuttalli, a total of 276 fecal samples from five populations at high altitudes (HAG, 2,800-4,100 m above sea level) and four populations at low altitudes (LAG, 5-1,000 m above sea level) were collected. PCR methods based on the ssrRNA gene were used to detect Entamoeba infection. Genotyping of E. nuttalli was performed based on six tRNA-linked short tandem repeat (STR) loci for further genetic analyses. The results revealed that Entamoeba infection (69.2%) was common in wild rhesus macaques in China, especially in LAG which had a significantly higher prevalence rate than that in HAG (P < 0.001). Three zoonotic species were identified: Entamoeba chattoni (60.9%) was the most prevalent species and distributed in all the populations, followed by Entamoeba coli (33.3%) and Entamoeba nuttalli (17.4%). In addition, a novel Entamoeba ribosomal lineage named RL13 (22.8%) was identified, and phylogenetic analysis revealed a close genetic relationship between RL13 and Entamoeba. hartmanni. Genotyping of E. nuttalli obtained 24 genotypes from five populations and further analysis showed E. nuttalli had a high degree of genetic differentiation (FST > 0.25, Nm < 1) between the host populations. The result of analysis of molecular variance (AMOVA) revealed that observed genetic differences mainly originate from differences among populations (FST = 0.91). Meanwhile, the phylogenetic tree showed that these genotypes of E. nuttalli were clustered according to geographical populations, indicating a significant phylogeographic distribution pattern. Considering the potential pathogenicity of E. nuttalli, attention should be paid to its risk of zoonotic transmission.

What does preferential viewing tell us about the neurobiology of recognition memory?

The two tests most widely used in nonhuman primates to assess the neurobiology of recognition memory produce conflicting results. Preferential viewing tests (e.g., visual paired comparison) produce robust impairments following hippocampal lesions, whereas matching tests (e.g., delayed nonmatching-to-sample) often show complete sparing. Here, we review the data, the proposed explanations for this discrepancy, and then critically evaluate those explanations. The most likely explanation is that preferential viewing tests are not a process-pure assessment of recognition memory, but also test elements of novelty-seeking, habituation, and motivation. These confounds likely explain the conflicting results. Thus, we propose that memory researchers should prefer explicit matching tests and readers interested in the neural substrates of recognition memory should give explicit matching tests greater interpretive weight.