Nonhuman primate

PURPOSE: CD137 is a T- and NK-cell costimulatory receptor involved in consolidating immunologic responses. The potent CD137 agonist urelumab has shown clinical promise as a cancer immunotherapeutic but development has been hampered by on-target off-tumor toxicities. A CD137 agonist targeted to the prostate-specific membrane antigen (PSMA), frequently and highly expressed on castration-resistant metastatic prostate cancer (mCRPC) tumor cells, could bring effective immunotherapy to this immunologically challenging to address disease...

BACKGROUND: High-precision neurosurgical targeting in nonhuman primates (NHPs) often requires presurgical anatomy mapping with noninvasive neuroimaging techniques (MRI, CT, PET), allowing for translation of individual anatomical coordinates to surgical stereotaxic apparatus. Given the varied tissue contrasts that these imaging techniques produce, precise alignment of imaging-based coordinates to surgical apparatus can be cumbersome. MRI-compatible stereotaxis with radiopaque fiducial markers offer a straight-forward and reliable solution, but existing commercial options do not fit in conformal head coils that maximize imaging quality...

The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia...

Primates live in a variety of social groupings and vary in the expression of species-typical behaviors depending upon social conditions. Coppery titi monkeys ( Plecturocebus cupreus ) are pair-bonding, territorial primates often used to study neurobiology and social behavior in captivity at the California National Primate Research Center (CNPRC). At the center, titi monkeys are housed in cages of standardized size. However, the number of cages--and thus families--per room varies based upon the room size (small or large)...

A Tn7-transposition approach was utilized for site-specific insertion of foreign genes into the genome of simian varicella virus (SVV), the causative agent of simian varicella in nonhuman primates. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) nucleocapsid (N) gene and receptor binding domain (RBD) of the spike gene were inserted into the ORF 14 region of the SVV genome cloned into a bacterial artificial chromosome and then transfected into Vero cells to generate the infectious recombinant SVV (rSVV)...

BACKGROUND: The article discusses the investigations into the nucleus of Perlia (NP), a spindle-shaped nucleus located in the dorsal aspect of the oculomotor complex. However, there is still debate over its exact location and function, with conflicting findings in nonhuman primates. Therefore, the current study aimed the describe the location, function, clinical and surgical implications of NP. METHODS: A systematic review was conducted to identify studies related to the following MeSH terms: "perlia nucleus" OR "nucleus of "perlia" OR "convergence nucleus" OR "nucleus of convergence" OR "Perlia's nucleus"...

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...

Linezolid is a drug with proven human antitubercular activity whose use is limited to highly drug-resistant patients because of its toxicity. This toxicity is related to its mechanism of action─linezolid inhibits protein synthesis in both bacteria and eukaryotic mitochondria. A highly selective and potent series of oxazolidinones, bearing a 5-aminomethyl moiety (in place of the typical 5-acetamidomethyl moiety of linezolid), was identified. Linezolid-resistant mutants were cross-resistant to these molecules but not vice versa...

The rhesus macaque (Macaca mulatta) is a crucial experimental animal that shares many genetic, brain organizational, and behavioral characteristics with humans. A macaque brain atlas is fundamental to biomedical and evolutionary research. However, even though connectivity is vital for understanding brain functions, a connectivity-based whole-brain atlas of the macaque has not previously been made. In this study, we created a new whole-brain map, the Macaque Brainnetome Atlas (MacBNA), based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data...

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions...

The nucleus accumbens (NAc) is a central component of the brain circuitry that mediates motivated behavior, including reward processing. Since the rewarding properties of social stimuli have a vital role in guiding behavior (both in humans and nonhuman animals), the nucleus accumbens is likely to contribute to the brain circuitry controlling social behavior. In rodents, prior studies have found that focal pharmacological inhibition of NAc and/or elevation of dopamine in NAc increases social interactions. However, the role of the NAc in social behavior in nonhuman primates remains unknown...

The ephemeral reward task involves providing subjects with a choice between two distinctive stimuli, A and B, each containing an identical reward. If A is chosen, the reward associated with A is obtained and the trial is over. If B is chosen, the reward associated with B is obtained but A remains, and the reward associated with A can be obtained as well. Thus, the reward-maximizing solution is to choose B first. Although cleaner fish (wrasse) and parrots easily acquire the optimal response by choosing B, paradoxically, several nonhuman primate species, as well as rats and pigeons, do not...

The ability to quickly perceive and interpret threatening facial expressions from others is critical for successfully maintaining group cohesion in social nonhuman primate species. Rapid detection of threatening or negative stimuli in the environment compared to neutral stimuli, referred to as an attentional bias toward threat, is adaptive in that faster threat detection can lead to greater survival outcomes. However, the evolutionary roots of attentional bias formation toward social threat are not well understood...

No abstract text is available yet for this article.

No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV and Hendra virus (HeV) G glycoprotein, m102.4, has been tested in a phase 1 trial and has been provided under compassionate use for both HeV and NiV exposures. NiV is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia. The mortality rate of NiV infection in humans ranges from 40% to more than 90%, making it a substantial public health concern...

The advent of mRNA for nucleic acid (NA) therapeutics has unlocked many diverse areas of research and clinical investigation. However, the shorter intracellular half-life of mRNA compared with other NAs may necessitate more frequent dosing regimens. Because lipid nanoparticles (LNPs) are the principal delivery system used for mRNA, this could lead to tolerability challenges associated with an accumulated lipid burden. This can be addressed by introducing enzymatically cleaved carboxylic esters into the hydrophobic domains of lipid components, notably, the ionizable lipid...

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 )...

The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs make the loci difficult to investigate with short reads. We characterize the structural diversity of MUC5AC and MUC5B by long-read sequencing and assembly of 206 human and 20 nonhuman primate (NHP) haplotypes. We find that human MUC5B is largely invariant (5761-5762aa); however, seven haplotypes have expanded VNTRs (6291-7019aa)...

Many different anesthetics cause loss of responsiveness despite having diverse underlying molecular and circuit actions. To explore the convergent effects of these drugs, we examined how ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and dexmedetomidine, an α2 adrenergic receptor agonist, affected neural oscillations in the prefrontal cortex of nonhuman primates. Previous work has shown that anesthesia increases phase locking of low-frequency local field potential activity across cortex...

Despite a five order of magnitude range in size, the brains of mammals share many anatomical and functional characteristics that translate into cortical network commonalities. Here we develop a machine learning framework to quantify the degree of predictability of the weighted interareal cortical matrix. Partial network connectivity data were obtained with retrograde tract-tracing experiments generated with a consistent methodology, supplemented by projection length measurements in a nonhuman primate (macaque) and a rodent (mouse)...